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Atlas of Genetics and Cytogenetics PTCH1 (patched homolog 1 (Drosophila)) in Oncology and Haematology Huret JL OPEN ACCESS JOURNAL AT INIST-CNRS Scope The Atlas of Genetics and Cytogenetics in Oncology and Haematology is a peer reviewed on-line journal in open access, devoted to genes, cytogenetics, and clinical entities in cancer, and cancer-prone diseases. It presents structured review articles (“cards”) on genes, leukaemias, solid tumours, cancer-prone diseases, and also more traditional review articles (“deep insights”) on the above subjects and on surrounding topics. It also present case reports in hematology and educational items in the various related topics for students in Medicine and in Sciences. Editorial correspondance Jean-Loup Huret Genetics, Department of Medical Information, University Hospital F-86021 Poitiers, France tel +33 5 49 44 45 46 or +33 5 49 45 47 67 [email protected] or [email protected] The Atlas of Genetics and Cytogenetics in Oncology and Haematology is published 4 times a year by ARMGHM, a non profit organisation. Philippe Dessen is the Database Director, and Alain Bernheim the Chairman of the on-line version (Gustave Roussy Institute – Villejuif – France). http://AtlasGeneticsOncology.org © ATLAS - ISSN 1768-3262 The PDF version of the Atlas of Genetics and Cytogenetics in Oncology and Haematology is a reissue of the original articles published in collaboration with the Institute for Scientific and Technical Information (INstitut de l’Information Scientifique et Technique - INIST) of the French National Center for Scientific Research (CNRS) on its electronic publishing platform I-Revues. Online and PDF versions of the Atlas of Genetics and Cytogenetics in Oncology and Haematology are hosted by INIST-CNRS. Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Editor Jean-Loup Huret (Poitiers, France) Volume 2, Number 1, January-March 1998 Table of contents Gene Section CALM (clathrin assembly lymphoid myeloid leukemia gene) Jean-Loup Huret 1 CAN (CAN protein, putative oncogene) Jean-Loup Huret 2 DDX10 (DEAD (Asp-Glu-Ala-Asp) box polypeptide 10) Jean-Loup Huret 3 DEK (DEK oncogene) Jean-Loup Huret 5 HOXA9 (homeobox A9) Jean-Loup Huret 6 NUP98 (nucleoporin 98 kDa) Jean-Loup Huret 7 BLM (Bloom) Jean-Loup Huret 8 TRIP11 (thyroid hormone receptor interactor 11) Jean-Loup Huret 9 FACC (Fanconi anaemia complementation group C) Jean-Loup Huret 10 FGFR3 (fibroblast growth factor receptor 3) Jacky Bonaventure 12 JAK2 (janus kinase 2) Jean-Loup Huret 14 RHOH (ras homolog gene family, member H) Sylvie Galiègue-Zouitina 15 Leukaemia Section Myelofibrosis with Myeloid Metaplasia (MMM); Idiopathic myelofibrosis; Agnogenic myeloid metaplasia Jean-Loup Huret Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 17 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Multiple myeloma Jean-Loup Huret 18 t(1;7)(p32;q34); t(1;14)(p32;q11); 1p32 rearrangements Jean-Loup Huret 20 t(3;13)(q27;q14) Jean-Loup Huret, Jean-Luc Laï 22 t(3;21)(q26;q22) Jean-Loup Huret, François Desangles 24 t(4;12)(q11-q21;p13) Jean-Loup Huret, Marina Lafage-Pochitaloff 26 t(5;12)(q33;p13) Jean-Loup Huret 27 t(6;9)(p23;q34) Jean-Loup Huret 29 t(10;11)(p13;q21) Jean-Loup Huret 32 t(11;14)(q13;q32) in multiple myeloma Jean-Loup Huret, Jean-Luc Laï 34 Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Genes Section Short Communication CALM (clathrin assembly lymphoid myeloid leukemia gene) Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France Published in Atlas Database: January 1998 Online version is available at: http://AtlasGeneticsOncology.org/Genes/CALM.html DOI: 10.4267/2042/32088 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity Implicated in Location: 11q14-21 t(10;11)(p13;q14-21) → CALM/AF10 and/or AF10/CALM Disease Yet to be well delineated; T-cell ALL. Prognosis . Uncertain (median survival 2 yrs?). Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Cytogenetics May well be confused with the t(10;11)(p12;q23), where MLL on 11q23 is involved, instead of CALM. DNA/RNA Hybrid/Mutated Gene Transcription 5' CALM - 3' AF10 and 5' AF10 - 3' CALM. Major mRNA: 4 kb; other: 3 and 9 kb. Abnormal Protein Protein Both CALM-AF10 and the reciprocal AF10-CALM are expressed. Description References 652 amino acids. Dreyling MH, Martinez-Climent JA, Zheng M, Mao J, Rowley JD, Bohlander SK. The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family. Proc Natl Acad Sci USA 1996 May 14;93(10):4804-9. Expression Wide. Function Kobayashi H, Hosoda F, Maseki N, Sakurai M, Imashuku S, Ohki M, Kaneko Y. Hematologic malignancies with the t(10;11)(p13;q21) have the same molecular event and a variety of morphologic or immunologic phenotypes. Genes Chromosomes Cancer 1997 Nov;20(3):253-9. Role in the integration of signals from different pathways (clathrin, phosphoinositols, receptormediated endocytosis). Homology This article should be referenced as such: With ap-3, a clathrin assembly protein (mouse). Huret JL. CALM (clathrin assembly lymphoid myeloid leukemia gene). Atlas Genet Cytogenet Oncol Haematol.1998;2(1):1. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 1 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Genes Section Short Communication CAN (CAN protein, putative oncogene) Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France Published in Atlas Database: January 1998 Online version is available at: http://AtlasGeneticsOncology.org/Genes/CAN.html DOI: 10.4267/2042/32089 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Disease Identity M2, M4 ANLL or MDS. Other names: CAIN; NUP214 (nuclear pore complex protein 214 kDa); nucleoporin Location: 9q34.3 Local order: more telomeric than ABL1; less than TAN1. Prognosis Remission difficult to obtain. Cytogenetics This chromosome anomaly may be over looked. Hybrid/Mutated Gene DNA/RNA 5' DEK - 3' CAN; chromosome 6 breakpoint clusters in a single intron. Description Abnormal Protein Spans on a 130 kb and more genomic segment. Head to tail DEK/CAN fusion protein (the alternative SET/CAN is exceptional); almost the entire DEK protein is fused to the C-terminal two-thirds of the CAN protein; nuclear localization. Transcription 7.5 kb mRNA. Protein Description t(6;9)(p23;q34)/AUL → SET/CAN (exceptional) 2090 amino acids; 214 kDa; dimerization domains (2 leucine zippers) and FG repeats; forms homodimers. References von Lindern M, Fornerod M, van Baal S, Jaeglé M, de Wit T, Buijs A, Grosveld G. The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA. Mol Cell Biol 1992 Apr;12(4):1687-97. Expression Thymus, bone marrow, spleen, kidney, testis, brain; apparently not in other tissues. Localisation Fornerod M, Boer J, van Baal S, Jaeglé M, von Lindern M, Murti KG, Davis D, Bonten J, Buijs A, Grosveld G. Relocation of the carboxyterminal part of CAN from the nuclear envelope to the nucleus as a result of leukemia-specific chromosome rearrangements. Oncogene 1995 May 4;10(9):1739-48. Nuclear membrane localisation. Function Nucleoporin: associated with the nuclear pore complex; role in nucleocytoplasmic transport processes and cell cycle progression. Fornerod M, Boer J, van Baal S, Morreau H, Grosveld G. Interaction of cellular proteins with the leukemia specific fusion proteins DEK-CAN and SET-CAN and their normal counterpart, the nucleoporin CAN. Oncogene 1996 Oct 17;13(8):1801-8. Homology C-term part of CAN has homologies with proteins of the nucleoporin family. This article should be referenced as such: Huret JL. CAN (CAN protein, putative oncogene). Atlas Genet Cytogenet Oncol Haematol.1998;2(1):2. Implicated in t(6;9)(p23;q34)/ANLL or MDS → DEK/CAN Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 2 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Genes Section Short Communication DDX10 (DEAD (Asp-Glu-Ala-Asp) box polypeptide 10) Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France Published in Atlas Database: January 1998 Online version is available at: http://AtlasGeneticsOncology.org/Genes/DDX10.html DOI: 10.4267/2042/32090 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity Other names: HRH-J8 Location: 11q22 Local order: telomeric to ATM. DDX10 (11q22) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome: contact [email protected]. Expression DNA/RNA Wide. Description Localisation At least 12 exons; spans more than a 200 kb region. Nucleolus (probable). Transcription Function Alternative splicing; 3.2 and 5.0 kb mRNA. Putative ATP-dependent DEAD box RNA helicase; possible role in ribosome assembly through rRNA processing. Protein Description Homology Contains 2 nuclear localization signals (NLS), a DEAD box (DEAD for: ASP-GLU_ALA-ASP). Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) SPB4 and DRS1 (yeast). 3 DDX10 (DEAD (Asp-Glu-Ala-Asp) box polypeptide 10) Huret JL Implicated in References inv(11)(p15q22)/MDS or ANLL → NUP98/DDX10 Savitsky K, Ziv Y, Bar-Shira A, Gilad S, Tagle DA, Smith S, Uziel T, Sfez S, Nahmias J, Sartiel A, Eddy RL, Shows TB, Collins FS, Shiloh Y, Rotman G. A human gene (DDX10) encoding a putative DEAD-box RNA helicase at 11q22-q23. Genomics 1996 Apr 15;33(2):199-206. Disease Therapy related MDS and ANLL; de novo ANLL. Arai Y, Hosoda F, Kobayashi H, Arai K, Hayashi Y, Kamada N, Kaneko Y, Ohki M. The inv(11)(p15q22) chromosome translocation of de novo and therapy-related myeloid malignancies results in fusion of the nucleoporin gene, NUP98, with the putative RNA helicase gene, DDX10. Blood 1997 Jun 1;89(11):3936-44. Hybrid/Mutated Gene 5' NUP98 - 3' DDX10. Abnormal Protein Fuses the GLFG repeat domains of NUP98 to the charged amino acids domain of DDX11. This article should be referenced as such: Huret JL. DDX10 (DEAD (Asp-Glu-Ala-Asp) box polypeptide 10). Atlas Genet Cytogenet Oncol Haematol.1998;2(1):3-4. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 4 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Genes Section Short Communication DEK (DEK oncogene) Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France Published in Atlas Database: January 1998 Online version is available at: http://AtlasGeneticsOncology.org/Genes/DEK_23.html DOI: 10.4267/2042/32091 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Disease Identity M2, M4 ANLL or MDS. Location: 6p23 Prognosis Remission difficult to obtain. Cytogenetics This chromosome anomaly may be over loocked. Hybrid/Mutated Gene 5' DEK - 3' CAN; chromosome 6 breakpoint clusters in a single intron. Abnormal Protein DEK (6p23) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome: contact [email protected]. Head to tail DEK/CAN fusion protein (the alternative SET/CAN is exceptional); almost the entire DEK protein fused to the C-terminal two-thirds of the CAN protein; nuclear localization. DNA/RNA References Description von Lindern M, Fornerod M, van Baal S, Jaeglé M, de Wit T, Buijs A, Grosveld G. The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA. Mol Cell Biol 1992 Apr;12(4):1687-97. Spans on a 40 kb genomic segment. Transcription 2.7 kb mRNA; coding sequence: 1.1 kb. Protein Fornerod M, Boer J, van Baal S, Jaeglé M, von Lindern M, Murti KG, Davis D, Bonten J, Buijs A, Grosveld G. Relocation of the carboxyterminal part of CAN from the nuclear envelope to the nucleus as a result of leukemia-specific chromosome rearrangements. Oncogene 1995 May 4;10(9):1739-48. Description 375 amino acids; 43 kDa; contains numerous acidic domains (Asp/Glu rich) and a nuclear localisation signal. Fornerod M, Boer J, van Baal S, Morreau H, Grosveld G. Interaction of cellular proteins with the leukemia specific fusion proteins DEK-CAN and SET-CAN and their normal counterpart, the nucleoporin CAN. Oncogene 1996 Oct 17;13(8):1801-8. Expression Wide. Localisation Fu GK, Grosveld G, Markovitz DM. DEK, an autoantigen involved in a chromosomal translocation in acute myelogenous leukemia, binds to the HIV-2 enhancer. Proc Natl Acad Sci USA 1997 Mar 4;94(5):1811-5. Potentially nuclear. Function Site specific DNA binding protein involved in transcriptional regulation and signal transduction. This article should be referenced as such: Huret JL. DEK (DEK oncogene). Atlas Genet Cytogenet Oncol Haematol.1998;2(1):5. Implicated in t(6;9)(p23;q34)/ANLL or MDS →DEK/CAN Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 5 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Genes Section Short Communication HOXA9 (homeobox A9) Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France Published in Atlas Database: January 1998 Online version is available at: http://AtlasGeneticsOncology.org/Genes/HOXA9.html DOI: 10.4267/2042/32092 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity Prognosis Other names: HOX1G (homeobox-1G) Location: 7p15 Cytogenetics Protein Hybrid/Mutated Gene Description Abnormal Protein Mean survival: 15 mths. Sole anomaly most often. 5' NUP98 - 3' HOXA9. Fuses the GLFG repeat domains of NUP98 to the HOXA9 homeobox. 129 amino acids; DNA binding domain (homeobox) in C-term. References Localisation Nuclear. Borrow J, Shearman AM, Stanton VP Jr, Becher R, Collins T, Williams AJ, Dubé I, Katz F, Kwong YL, Morris C, Ohyashiki K, Toyama K, Rowley J, Housman DE. The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9. Nat Genet 1996 Feb;12(2):159-67. Function Sequence specific transcription factor; role during embryonic development (patterning); HOX genes are also expressed in adult tissues, including blood cells; probable role in blood cell differentiation. Nakamura T, Largaespada DA, Lee MP, Johnson LA, Ohyashiki K, Toyama K, Chen SJ, Willman CL, Chen IM, Feinberg AP, Jenkins NA, Copeland NG, Shaughnessy JD Jr. Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia. Nat Genet 1996 Feb;12(2):154-8. Homology With class 1 homeodomain proteins. Implicated in t(7;11)(p15;p15)/ANLL → NUP98/HOXA9 Lawrence HJ, Helgason CD, Sauvageau G, Fong S, Izon DJ, Humphries RK, Largman C. Mice bearing a targeted interruption of the homeobox gene HOXA9 have defects in myeloid, erythroid, and lymphoid hematopoiesis. Blood 1997 Mar 15;89(6):1922-30. Disease This article should be referenced as such: M2-M4 ANLL mostly; occasionally: CML-like cases. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) Huret JL. HOXA9 (homeobox A9). Atlas Genet Cytogenet Oncol Haematol.1998;2(1):6. 6 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Genes Section Short Communication NUP98 (nucleoporin 98 kDa) Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France Published in Atlas Database: January 1998 Online version is available at: http://AtlasGeneticsOncology.org/Genes/NUP98.html DOI: 10.4267/2042/32093 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Hybrid/Mutated Gene Identity 5' NUP98 - 3' HOXA9. Location: 11p15 Abnormal Protein DNA/RNA Fuses the GLFG repeat domains of NUP98 to the HOXA9 homeobox. Transcription 3.6, 6.5, 7.0 kb mRNA. inv(11)(p15q22)/MDS or ANLL → NUP98/DDX10 Protein Disease Description Therapy related MDS and ANLL; de novo ANLL. 920 amino acids; 97 kDa; contains repeated motifs (GLFG and FG) in N-term and a RNA binding motif in C-term. 5' NUP98 - 3' DDX10. Hybrid/Mutated Gene Abnormal Protein Fuses the GLFG repeat domains of NUP98 to the acidic domain of DDX10. Expression Wide. References Localisation Borrow J, Shearman AM, Stanton VP Jr, Becher R, Collins T, Williams AJ, Dubé I, Katz F, Kwong YL, Morris C, Ohyashiki K, Toyama K, Rowley J, Housman DE. The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9. Nat Genet 1996 Feb;12(2):159-67. Nuclear membrane localisation. Function Nucleoporin: associated with the nuclear pore complex; role in nucleocytoplasmic transport processes. Nakamura T, Largaespada DA, Lee MP, Johnson LA, Ohyashiki K, Toyama K, Chen SJ, Willman CL, Chen IM, Feinberg AP, Jenkins NA, Copeland NG, Shaughnessy JD Jr. Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia. Nat Genet 1996 Feb;12(2):154-8. Homology Member of the GLFG nucleoporins. Implicated in Arai Y, Hosoda F, Kobayashi H, Arai K, Hayashi Y, Kamada N, Kaneko Y, Ohki M. The inv(11)(p15q22) chromosome translocation of de novo and therapy-related myeloid malignancies results in fusion of the nucleoporin gene, NUP98, with the putative RNA helicase gene, DDX10. Blood 1997 Jun 1;89(11):3936-44. t(7;11)(p15;p15)/ANLL → NUP98/HOXA9 Disease M2-M4 ANLL mostly; occasionally: CML-like cases. Powers MA, Forbes DJ, Dahlberg JE, Lund E. The vertebrate GLFG nucleoporin, Nup98, is an essential component of multiple RNA export pathways. J Cell Biol 1997 Jan 27;136(2):241-50. Prognosis Mean survival: 15 mths. Cytogenetics Sole anomaly most often. This article should be referenced as such: Huret JL. NUP98 (nucleoporin 98 kDa). Atlas Genet Cytogenet Oncol Haematol.1998;2(1):7. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 7 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Genes Section Short Communication BLM (Bloom) Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France Published in Atlas Database: February 1998 Online version is available at: http://AtlasGeneticsOncology.org/Genes/BLM109.html DOI: 10.4267/2042/32095 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity Implicated in Location: 15q26.1 Bloom syndrome DNA/RNA Disease Bloom syndrome is a chromosome instability syndrome/cancer prone disease (at risk of numerous, early occurring cancers of various types). Transcription 4.4 kb mRNA. Prognosis Protein 1/3 of patients are dead at mean age 24 yrs, and the mean age of the 2/3 remaining alive patients is 22 yrs. Description Cytogenetics 1417 amino acids; ATP binding in amino acid 689-696; DEAH box in 795-798; two putative nuclear localization signals in the C-term in 1334-1349. Chromatid/chromosome breaks; triradial and quadriradial figures, highly elevated spontaneous sister chromatid exchange rate. Localisation References Nuclear. Ellis NA, Groden J, Ye TZ, Straughen J, Lennon DJ, Ciocci S, Proytcheva M, German J. The Bloom's syndrome gene product is homologous to RecQ helicases. Cell 1995 Nov 17;83(4):65566. Function DNA helicase; probable role in DNA replication and repair; possibly also in transcription regulation. Ellis NA, German J. Molecular genetics of Bloom's syndrome. Hum Mol Genet 1996;5 Spec No:1457-63. Homology Foucault F, Vaury C, Barakat A, Thibout D, Planchon P, Jaulin C, Praz F, Amor-Gueret M. Characterization of a new BLM mutation associated with a topoisomerase II alpha defect in a patient with Bloom's syndrome. Hum Mol Genet 1997 Sep;6(9):1427-34. Homologous to RecQ helicases, a subfamily of DExH box-containing DNA and RNA helicases; in particular, similarity with the gene mutated in Werner syndrome, WRN, another member of the RecQ family; Werner syndrome is another cancer-prone disease. Kaneko H, Orii KO, Matsui E, Shimozawa N, Fukao T, Matsumoto T, Shimamoto A, Furuichi Y, Hayakawa S, Kasahara K, Kondo N. BLM (the causative gene of Bloom syndrome) protein translocation into the nucleus by a nuclear localization signal. Biochem Biophys Res Commun 1997 Nov 17;240(2):348-53. Mutations Germinal The mutated BLM protein is retained in the cytoplasm or both in the cytoplasm and the nucleus, while the normal protein is nuclear. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) This article should be referenced as such: Huret JL. BLM (Bloom). Atlas Genet Cytogenet Oncol Haematol.1998;2(1):8. 8 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Genes Section Short Communication TRIP11 (thyroid hormone receptor interactor 11) Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France Published in Atlas Database: February 1998 Online version is available at: http://AtlasGeneticsOncology.org/Genes/CEV14.html DOI: 10.4267/2042/32096 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity Implicated in Location: 14q32 t(5;14)(q33;q32)/ANLL → CEV14/PDGFRb DNA/RNA Disease Transcription Poorly known: 1 case of ANLL. Major transcripts: 7, 9 and 10.5 kb; coding sequence: 2.2 kb. Cytogenetics Protein Hybrid/Mutated Gene Description Abnormal Protein Found as an additional anomaly. 5' CEV14 - 3' PDGFRb. 729 amino acids; contains a N-term leucine zipper and a C-term putative thyroid hormone receptor interacting domain. Leucine zipper from CEV14 fused to the transmembrane domain and the Tyr kinase domain of PDGFRb. Expression References Is wide; high expression in heart, muscle, pancreas; found expressed in hematopoietic cell lines. Abe A, Emi N, Tanimoto M, Terasaki H, Marunouchi T, Saito H. Fusion of the platelet-derived growth factor receptor beta to a novel gene CEV14 in acute myelogenous leukemia after clonal evolution. Blood 1997 Dec 1;90(11):4271-7. Function May be a transcriptional factor. This article should be referenced as such: Huret JL. TRIP11 (thyroid hormone receptor interactor 11). Atlas Genet Cytogenet Oncol Haematol.1998;2(1):9. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 9 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Genes Section Short Communication FACC (Fanconi anaemia complementation group C) Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France Published in Atlas Database: February 1998 Online version is available at: http://AtlasGeneticsOncology.org/Genes/FACC101.html DOI: 10.4267/2042/32097 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Function Identity Peak expression during the G2/M transition; binds to cdc2 (mitotic cyclin-dependent kinase); probably involved in basic aspect(s) of the cell protection against DNA damages: role in the cell cycle regulation and/or in DNA repair and/or in the prevention of cellular apoptosis; binds to FAA, the protein encoded by FA1 (Fanconi anaemia complementation group A), the dimer being found in the cytoplasm and the nucleus. Other names: FAC Location: in 9q22.3 Local order: next to PTCH and XPAC. Homology No known homology. Mutations Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Germinal DNA/RNA Mainly nucleotide substitutions, dispersed along the coding sequence. Description Implicated in 14 exons; spans 80 kb. Fanconi anaemia; FACC is implicated in the FA complementation group C Transcription mRNA of 2.3, 3.2, and 4.6 kb (variable 3' untranslated region, alternative splicing, exon skipping). Disease Fanconi anaemia is a chromosome instability syndrome/cancer prone disease (at risk of leukaemia). Protein Prognosis Poor; mean survival is 16 years: patients die of bone marrow failure (infections, haemorrhages), leukaemia, or androgen therapy related liver tumours. Description 558 amino acids; 63 kDa; alpha helical structure in Cterm. Cytogenetics Expression Spontaneous, chromatid/chromosome breaks; increased rate of breaks compared to control, when induced by breaking agent. Wide, in particular in the bones. Localisation References Cytoplasmic at any cell-cycle stage. Strathdee CA, Gavish H, Shannon WR, Buchwald M. Cloning of cDNAs for Fanconi's anaemia by functional complementation. Nature 1992;356:763-767. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 10 FACC (Fanconi anaemia complementation group C) Huret JL Gibson RA, Buchwald M, Roberts RG, Mathew CG. Characterisation of the exon structure of the Fanconi anaemia group C gene by vectorette PCR. Hum Mol Genet 1993;2:3538. Kupfer GM, Näf D, Suliman A, Pulsipher M, D'Andrea AD. The Fanconi anaemia proteins, FAA and FAC, interact to form a nuclear complex. Nat Genet 1997 Dec;17(4):487-90. D'Andrea AD, Grompe M. Molecular biology of Fanconi anemia: implications for diagnosis and therapy. Blood 1997;90(5):1725-36. This article should be referenced as such: Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) Huret JL. FACC (Fanconi anaemia complementation group C). Atlas Genet Cytogenet Oncol Haematol.1998;2(1):10-11. 11 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Genes Section Mini Review FGFR3 (fibroblast growth factor receptor 3) Jacky Bonaventure Unité INSERM 393, Hopital Necker-Enfants Malades, 149 rue de Sèvres 75743, Paris Cedex 15, France Published in Atlas Database: February 1998 Online version is available at: http://AtlasGeneticsOncology.org/Genes/FGFR99.html DOI: 10.4267/2042/32098 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity Transcription Location: 4p16.3 Local order: centromere - IT 15 - FGFR 3 - IDUA - 4.0 kb mRNA; large 3' untranslated region (1.4 kb); alternative splicing of exons 7 and 8 gives rise to two isoforms IIIb and IIIc. MYL 5 - ZNF 141 - telomere. Protein DNA/RNA Description 806 amino acids; 115 kDa; tyrosine kinase receptor; contains three major domains: an extracellular domain with 3 Ig-like loops, a highly hydrophobic transmembrane domain (22 amino acids) and an intracellular domain with tyrosine kinase activity. Expression Mostly in brain, cartilage, liver, inner ear, kidney. Localisation Plasma membrane. Function FGF receptor with tyrosine kinase activity; binding of ligand (FGF) induces receptor dimerization, autophosphorylation and signal transduction. c-FGFR3 (4p16.3) in normal cells: PAC 1054L13 (above) and PAC 1174P18 (below) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Description Homology 16.5 kb; 19 exons; exon 1 unknown in human. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) With other FGFR (1, 2 and 4); Cek 2 in chicken. 12 FGFR3 (fibroblast growth factor receptor 3) Bonaventure J Implicated in References t(4;14)(p16.3;q32.3)/multiple myeloma → FGFR3/IgH Rousseau F, Bonaventure J, Legeai-Mallet L, Pelet A, Rozet JM, Maroteaux P, Le Merrer M, Munnich A. Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. Nature 1994 Sep 15;371(6494):252-4. Disease Chesi M, Nardini E, Brents LA, Schröck E, Ried T, Kuehl WM, Bergsagel PL. Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3. Nat Genet 1997 Jul;16(3):260-4. Plasma cell leukaemia and multiple myeloma. Prognosis Unknown: found in 11 cases, but with no data on clinics. Richelda R, Ronchetti D, Baldini L, Cro L, Viggiano L, Marzella R, Rocchi M, Otsuki T, Lombardi L, Maiolo AT, Neri A. A novel chromosomal translocation t(4; 14)(p16.3; q32) in multiple myeloma involves the fibroblast growth-factor receptor 3 gene. Blood 1997 Nov 15;90(10):4062-70. Abnormal Protein No fusion protein, but promoter exchange between both partner genes. Oncogenesis Webster MK, Donoghue DJ. FGFR activation in skeletal disorders: too much of a good thing. Trends Genet 1997 May;13(5):178-82. Overexpression and activation of FGFR 3 provides an oncogenic signal. Squeletal dysplasia (inborn diseases) This article should be referenced as such: Disease Bonaventure J. FGFR3 (fibroblast growth factor receptor 3). Atlas Genet Cytogenet Oncol Haematol.1998;2(1):12-13. Hypochondroplasia, achondroplasia, thanatophoric dwarfism (TD I and II), Crouzon syndrome with acanthosis nigricans and coronal craniosynostosis; endochondral and membranous ossification defects are caused by recurrent missense mutations. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 13 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Genes Section Short Communication JAK2 (janus kinase 2) Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France Published in Atlas Database: February 1998 Online version is available at: http://AtlasGeneticsOncology.org/Genes/JAK98.html DOI: 10.4267/2042/32099 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity Implicated in Location: 9p24 t(9;12)(p24;p13)/acute leukaemias → JAK2/ETV6 DNA/RNA Prognosis Description Unknown. 24 exons spanning 140 kb; 4.2 kb cDNA. Hybrid/Mutated Gene Protein 5' ETV6 - 3' JAK2. Description N-term- HLH from ETV6 fused to the the tyrosine Kinase c-term domains of JAK2. Abnormal Protein 1132 amino acids. Oncogenesis Expression It may be speculated that the HLH domain of ETV6 provides a dimerization interface to the kinase domain of JAK2, which activates JAK2. Wide. Localisation References Possibly membrane associated. Function Lacronique V, Boureux A, Valle VD, Poirel H, Quang CT, Mauchauffe M, Berthou C, Lessard M, Berger R, Ghysdael J, Bernard OA. A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. Science 1997;278:1309-12. Tyrosine kinase; associates with the intracellular domains of cytokine receptors; signal transduction. Homology Peeters P, Raynaud SD, Cools J, Wlodarska I, Grosgeorge J, Philip P, Monpoux F, Van, Rompaey L, Baens M, Van den Berghe H, Marynen P. Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia. Blood 1997;90:2535-40. >90% identical to the mouse and the rat JAK2 homologs; belongs to the janus kinase subfamilly (JAK1, JAK3, TYK2). This article should be referenced as such: Huret JL. JAK2 (janus kinase 2). Atlas Genet Cytogenet Oncol Haematol.1998;2(1):14. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 14 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Genes Section Mini Review RHOH (ras homolog gene family, member H) Sylvie Galiègue-Zouitina U.124 INSERM, I.R.C.L., Place de Verdun, 59045 Lille Cedex, France Published in Atlas Database: February 1998 Online version is available at: http://AtlasGeneticsOncology.org/Genes/RHOH93.html DOI: 10.4267/2042/32100 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Localisation Identity Plasmic membrane. Other names: TTF (translocation three four); ARHH Location: 4p13 Function Small GTPase of the Rho subfamily; involved in signal transduction and cytoskeletal reorganization. Homology With all GTPases of the Ras superfamily. Implicated in t(3;4)(q27;p13)/NHL → BCL6/RHOH Disease Follicular NHL. RHOH (4p13) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome: contact [email protected]. Cytogenetics Observed as a secondary anomaly. DNA/RNA Hybrid/Mutated Gene Description 5' RHOH - 3' BCL6 and 5' BCL6 - 3' RHOH, are leading to two fusion transcripts. Spans on a 35 kb genomic fragment; two exons separated by a large intron; small GTPase encoding gene. Abnormal Protein Transcription t(4;14)(p13;q32)/multiple myeloma → RHOH/? No fusion protein, but promoter exchange between both partner genes. 2.2 kb mRNA; coding sequence: 575 bp, located in the second exon. Disease Protein Multiple myeloma. Description Still unknown: only 1 available case. 191 amino acids; 21 kDa; contains a GTP binding motif, a GTPase activity site, and a membrane localisation signal (CAAX box) in the very C-term. Cytogenetics Expression Not yet known (under study). Restricted to the hemopoietic tissues. Abnormal Protein Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) Prognosis Observed as a unique anomaly. Hybrid/Mutated Gene No fusion protein. 15 RHOH (ras homolog gene family, member H) Galiègue-Zouitina S Dallery-Prudhomme E, Roumier C, Denis C, Preudhomme C, Kerckaert JP, Galiegue-Zouitina S. Genomic structure and assignment of the RhoH/TTF small GTPase gene (ARHH) to 4p13 by in situ hybridization. Genomics 1997 Jul 1;43(1):8994. References Dallery E, Galiegue-Zouitina S, Collyn-d'Hooghe M, Quief S, Denis C, Hildebrand MP, Lantoine D, Deweindt C, Tilly H, Bastard C, et al. TTF, a gene encoding a novel small G protein, fuses to the lymphoma-associated LAZ3 gene by t(3;4) chromosomal translocation. Oncogene 1995 Jun 1;10(11):2171-8. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) This article should be referenced as such: Galiègue-Zouitina S. RHOH (ras homolog gene family, member H). Atlas Genet Cytogenet Oncol Haematol.1998;2(1):15-16. 16 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Leukaemia Section Short Communication Myelofibrosis with Myeloid Metaplasia (MMM) Idiopathic myelofibrosis Agnogenic myeloid metaplasia Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France Published in Atlas Database: January 1998 Online version is available at: http://AtlasGeneticsOncology.org/Anomalies/Myelofib.html DOI: 10.4267/2042/32101 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Clinics and pathology Cytogenetics Disease Cytogenetics, morphological Chronic myeloproliferative syndrome. An abnormal karyotype is found in 40% of cases at diagnosis: der(1), in particular partial trisomy 1, del(5q) or -5, -7, +8, +9, del(13q), del(20q) are seen solely or simultaneously in 5-10% of cases with chromosome anomalies, and other (various) anomalies in 40%. Phenotype / cell stem origin Pluripotent stem cell is involved. Epidemiology Annual incidence: 2/106; slightly more frequent in males; age is usually over 50 yrs. Genes involved and Proteins Clinics Asymptomatic for a long time, revealed by symptoms related to the splenomegaly, or by anaemia/asthenia; splenomegaly is the major sign; hepatomegaly in 50%; blood data: anisocytosis, poikylocytosis (as tear drops, are characteristic); anaemia is frequent; hyperleucocytosis in 60%; thrombocytosis may be present; erythromyelemia. Note: genes involved are unkown. Cytology Groupe Français de Cytogénétique Hématologique. Cytogenetics of acutely transformed chronic myeloproliferative syndromes without a Philadelphia chromosome. Cancer Genet Cytogenet 1988 Jun;32(2):157-68. To be noted 'Acute myelofibrosis' is a megakaryoblastic leukaemia (M7 ANLL) with prominent fibrosis. References Bone marrow: fibrosis is major (fibrosis is a secondary event in this disease), while there is extramedullary hematopoiesis (myeloid metaplasia) in the spleen, the liver, and anywhere (e.g. skin). Mertens F, Johansson B, Heim S, Kristoffersson U, Mitelman F. Karyotypic patterns in chronic myeloproliferative disorders: report on 74 cases and review of the literature. Leukemia 1991 Mar;5(3):214-20. Prognosis Evolution: this is a chronic disease, with a proliferative stage followed by a pancytopenic stage; pancytopenia and portal hypertension are the major causes of death in this disease; evolution towards ANLL is found in 1520% of cases; prognosis: is highly variable; survival is frequently over 10-15 yrs, but death occurs within a year in some cases; cases with pancytopenia directly at diagnosis bear a worse prognosis; probable prognostic factors are: the presence of an abnormal karyotype and a low haemoblobin level, possibly a low platelets count and a high WBC, a higher age, and hepatomegaly. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) Dupriez B, Morel P Demory JL, Lai JL, Simon M, Plantier I, Bauters F. Prognostic factors in agnogenic myeloid metaplasia: a report on 195 cases with a new scoring system. Blood 1996 Aug 1;88(3):1013-8. Reilly JT, Snowden JA, Spearing RL, Fitzgerald PM, Jones N, Watmore A, Potter A. Cytogenetic abnormalities and their prognostic significance in idiopathic myelofibrosis: a study of 106 cases. Br J Haematol 1997;98:96-102. This article should be referenced as such: Huret JL. Myelofibrosis with Myeloid Metaplasia (MMM); Idiopathic myelofibrosis; Agnogenic myeloid metaplasia. Atlas Genet Cytogenet Oncol Haematol.1998;2(1):17. 17 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Leukaemia Section Mini Review Multiple myeloma Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France Published in Atlas Database: January 1998 Online version is available at: http://AtlasGeneticsOncology.org/Anomalies/MMULID2038.html DOI: 10.4267/2042/32102 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology as an important prognostic factor: median survival in case of a normal karyotype could be 4 yrs vs 1 yr in case of -13/del(13q) and/or 11q rearrangements (the chromosome anomalies with the worst prognostic impact). Clinics and pathology Disease Multiple myeloma (MM) is a malignant plasma cell proliferation. Cytogenetics Phenotype / cell stem origin Phenotype of mature terminally differenciated B-cell, but also with CD56 expression, which is not found in normal plasma cells; CD38+ CD40+. Cytogenetics, morphological Cytogenetic information is limited, as the malignant cells have a low spontaneous proliferative activity; abnormal karyotypes are found in 30-50% of cases, more often in advanced stages than in newly diagnosed patients (is this because chromosome abnormalities are secondary events, or because malignant cells have an increased proliferative activity in advanced stages: see below); Karyotypes are complex; hyperploidy is found in 2/3 of cases; karyotypes may evolve from normal to abnormal during course of the disease; monosomy 13 or del(13q) is found in about 40% of MM cases with an abnormal karyotype; structural (and variable) anomalies of chromosome 1 are found in 30-40% of cases; 14q rearrangements: 25% of cases; 11q abnormalities 20 %; t(11;14) representing 10%; 6q anomalies represent 15% of cases. Epidemiology Multiple myeloma's annual incidence: 30/106; i.e. around 1% of malignancies in adults and 10% of haematologic malignancies; mean age: 62 yrs. Clinics Patients may be asymptomatic at the time of diagnosis; bone pain; susceptibility to infections; renal failure; neurologic dysfunctions. Pathology MM staging: stage I: tumour cell mass < 0.6 X 1012/m2; Hb> 10 g/dl; serum calcium ¾ 120 mg/l; no bone lesion; low monoclonal Ig rate (IgG < 50 g/l, IgA < 30 g/l, BJ urine < 4 g/day); stage II: fitting neither stage I nor stage II; stage III: tumour cell mass > 1.2 X 1012/m2; Hb < 8.5 g/dl and/or serum calcium > 120 mg/l and/or advanced lytic bone lesions and/or high monoclonal Ig rate (IgG > 70 g/l, IgA > 50 g/l, BJ urine > 12 g/day). Cytogenetics, molecular FISH is indicated, as metaphases are arduous to obtain in such a disease implicating mature cells, and tend to show that most cases bear chromosome anomalies, irrespective of the disease staging. Treatment None before onset of symptoms; chemotherapy or BMT afterwards. Prognosis Genes involved and Proteins Evolution: multiple myeloma can evolve towards plasma cell leukaemia, where plasma cell count is greater than 2000/mm3; survival is highly variable (median is around 3 yrs); prognosis is according to the staging and other parameters (such as age, serum albumin, b2 microglobulin, C-reactive protein, and plasma cell labeling index); the karyotype is emerging Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) C-MYC Location: 8q24 Note: Overexpression (mainly without rearrangement or amplification) correlated with increased tumour cell burden. RAS mutations (found in 20% of cases) and P53 mutations are associated with advanced disease. 18 Multiple myeloma Huret JL RB1 References Location: 13q14 Note: RB1 is deleted in more than 1/3 of cases. Rosen L, Vescio R, Berenson JR. Multiple myeloma and chronic lymphocytic leukemia. Curr Opin Hematol 1995 Jul;2(4):275-82. (Review). BCL1 Feinman R, Sawyer J, Hardin J, Tricot G. Cytogenetics and molecular genetics in multiple myeloma. Hematol Oncol Clin North Am 1997 Feb;11(1):1-25. (Review). Location: 11q13 Note: BCL1 is involved in t(11;14) cases. This article should be referenced as such: Huret JL. Multiple myeloma. Atlas Genet Cytogenet Oncol Haematol.1998;2(1):18-19. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 19 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Leukaemia Section Mini Review t(1;7)(p32;q34) t(1;14)(p32;q11) 1p32 rearrangements Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France Published in Atlas Database: January 1998 Online version is available at: http://AtlasGeneticsOncology.org/Anomalies/t0114.html DOI: 10.4267/2042/32103 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity Clinics and pathology Note: the two chromosome anomalies are variants of Disease each other, and they share identical features. T- cell ALL. Epidemiology Rare findings; t(1;14) is found in approximately 3% of T-ALL; t(1;7) is rarer (status 3: < 5 cases); however, TAL1 rearrangements, alltogether (being mostly submicroscopic deletions without visible 1p32 involvement), occurs in 15-25% of T-ALL; male predominance (as is classical in T-cell ALL). Clinics Organomegaly; high WBC (median 200 X 109/l). t(1;14)(p32;q11) G-banding - Courtesy Diane H. Norback, Eric B. Johnson, and Sara Morrison-Delap, UW Cytogenetic Services. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 20 t(1;7)(p32;q34). t(1;14)(p32;q11). 1p32 rearrangements Huret JL Cytogenetics Result of the chromosomal anomaly Additional anomalies t(1;14) is found solely in about half cases, and accompanied by del(6q) in nearly half cases as well. Fusion protein Genes involved and Proteins In most cases (breakpoints between exons 2B and 3 of TAL1), 3' TAL1 joins variable and diversity segments of TCR on der(14); in the few cases where the breakpoint is within exon 6 of TAL1 or 3' from it, constant segments of TCR join TAL1 on der(1). Description TAL1 Location: 1p32 DNA / RNA References Complex alternate splicing. Protein Bash RO, Crist WM, Shuster JJ, Link MP, Amylon M, Pullen J, Carroll AJ, Buchanan GR, Smith RG, Baer R. Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study. Blood 1993 Apr 15;81(8):2110-7. Contains a basic Helix-Loop-Helix (DNA binding) domain; forms heterodimers; transcription factor; role in haematopoietic cell differentiation. TRA/D Location: 14q11 in the case of a t(1;14). This article should be referenced as such: TRB Huret JL. t(1;7)(p32;q34). t(1;14)(p32;q11). rearrangements. Atlas Genet Cytogenet Haematol.1998;2(1):20-21. Location: 7q35 in the case of a t(1;7). Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 21 1p32 Oncol Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Leukaemia Section Short Communication t(3;13)(q27;q14) Jean-Loup Huret, Jean-Luc Laï Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France (JLH); INSERM Unité 524, Institut de Recherche sur le Cancer de Lille, Lille, France (JLL) Published in Atlas Database: January 1998 Online version is available at: http://AtlasGeneticsOncology.org/Anomalies/t0313.html DOI: 10.4267/2042/32104 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity t(3;13)(q27;q14-21), t(14;18)(q32;q21) G-banding - Courtesy Jean-Luc Lai. Clinics and pathology Cytogenetics Disease Cytogenetics, morphological NHL Found twice (out of three occurrence) as a secondary anomaly: following the well known t(8;14)(q24;q32) and t(14;18)(q32;q21). Phenotype / cell stem origin Found in various types of NHL (e.g. Burkitt's lymphoma and follicular lymphoma); the translocation is therefore likely to be a secondary event in the course of the disease. Additional anomalies del(6q) found in 2 of 3 cases; the karyotype may be complex. Epidemiology Only 3 cases available to date; all three are adult female patients. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 22 t(3;13)(q27;q14) Huret JL, Laï JL Genes involved and Proteins References BCL6 Laï JL, Daudignon A, Kerckaert JP, Galiegue-Zouitina S, Detourmignies L, Morel P, Bauters F, Fenaux P. Translocation (3;13)(q27;q14): a nonrandom and probably secondary structural change in non-Hodgkin lymphomas. Cancer Genet Cytogenet 1998 Jun;103(2):140-3. Location: 3q27 L-plastin Location: 13q14-21 This article should be referenced as such: Huret JL, Laï JL. t(3;13)(q27;q14). Atlas Genet Cytogenet Oncol Haematol.1998;2(1):22-23. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 23 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Leukaemia Section Mini Review t(3;21)(q26;q22) Jean-Loup Huret, François Desangles Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France (JLH); Laboratoire de Biologie, Hôpital du Val de Grâce, 75230 Paris, France (FD) Published in Atlas Database: January 1998 Online version is available at: http://AtlasGeneticsOncology.org/Anomalies/t0321.html DOI: 10.4267/2042/32105 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity t(3;21)(q26;q22) G-banding (top left) - Courtesy Diane H. Norback, Eric B. Johnson, and Sara Morrison-Delap, Cytogenetics at the Waisman, and R-banding (bottom left) with diagrams - courtesy Peter Meeus. Clinics and pathology Epidemiology Disease Clinics CML-BC of myeloid type (as far as 1% of cases); ANLL and MDS, often therapy related. May be secondary antitopoisomerase II. Phenotype / cell stem origin Cytology >1% of ANLL; all ages represented. toxic exposure, as to Presence of micromegakarycytes, both in BC-CML and MDS/ANLL cases; low platelet count and dysmyelopoiesis in MDS/ANLL cases. No FAB specificity. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) to 24 t(3;21)(q26;q22) Huret JL, Desangles F Prognosis Fusion protein Poor survival. Description AML1-EVI1: 180 kDa; breakpoint after exon 5 or 6 in AML1, at the very 5' end of EVI1 → translocation protein includes N-term AML1 with the Runt domain and most of the gene EVI1, from the second untranslated exon to C-term, which includes the 2 zinc fingers. Genes involved and Proteins EVI1 Location: 3q26 Note: or EAP (129 amino acids; putative nuclear localization signal) and/or MDS1 (rich in: proline, serine, and acidic residues), both also in 3q26. Oncogenesis Chimeric transcription factor with the dual functions of AML1 and EVI1: differentiation block (due to Runt) and stimulation of proliferation (from the zn fingers). AML1 Location: 21q22 DNA / RNA References Transcription is from telomere to centromere. Protein Horsman DE, Gascoyne RD, Barnett MJ. Acute leukemia with structural rearrangements of chromosome 3. Leuk Lymphoma 1995 Feb;16(5-6):369-77. (Review). Contains a Runt domain and, in the C-term, a transactivation domain; forms heterodimers; widely expressed; nuclear localisation; transcription factor (activator) for various hematopoietic-specific genes. Nucifora G, Rowley JD. AML1 and the 8;21 and 3;21 translocations in acute and chronic myeloid leukemia. Blood 1995 Jul 1;86(1):1-14. (Review). Secker-Walker LM, Mehta A, Bain B. Abnormalities of 3q21 and 3q26 in myeloid malignancy: a United Kingdom Cancer Cytogenetic Group study. Br J Haematol 1995 Oct;91(2):490501. Results of the chromosomal anomaly Lo Coco F, Pisegna S, Diverio D. The AML1 gene: a transcription factor involved in the pathogenesis of myeloid and lymphoid leukemias. Haematologica 1997 May-Jun;82(3):36470. (Review). Hybrid gene Description Fusion gene: on the der(3); 5' AML1 - 3' EVI1 (or 5' AML1 - 3' EAP/MDS1). Mitani K. Molecular mechanism of blastic crisis in chronic myelocytic leukemia. Leukemia 1997 Apr;11 Suppl 3:503-5. This article should be referenced as such: Huret JL, Desangles F. t(3;21)(q26;q22). Cytogenet Oncol Haematol.1998;2(1):24-25. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 25 Atlas Genet Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Leukaemia Section Short Communication t(4;12)(q11-q21;p13) Jean-Loup Huret, Marina Lafage-Pochitaloff Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France (JLH); Laboratoire de Cytogénétique Hématologique, Institut Paoli-Calmettes, Marseille, France (MLP) Published in Atlas Database: January 1998 Online version is available at: http://AtlasGeneticsOncology.org/Anomalies/t0412.html DOI: 10.4267/2042/32106 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity Cytogenetics Note: it is likely that breakpoints are heterogeneous, Additional anomalies with 2 distinct entities: t(4;12)(q11-12;p13) in ANLL, and t(4;12)(q13-21;p13) in ALL to be delineated. None in 5/12 cases (all 5 cases are ANLL); del(6q) has recurrently been found in ALL; -7 would be recurrent if only 1 entity exists; the karyotype in ALL cases can be complex. Clinics and pathology Disease Genes involved and Proteins ANLL and therapy related AL cases with t(4;12)(q1112;p13); B-cell ALL cases seem to have a more distal breakpoint in 4q13 or 21. ETV6 Location: 12p13 Phenotype / cell stem origin DNA / RNA ANLL cases: M0, M1, and other subtypes; often CD7+; a stem cell may be involved; ALL cases are CD10+. 9 exons; alternate splicing. Protein Epidemiology Contains a Helix-Loop-Helix and ETS DNA binding domains; wide expression; nuclear localisation; ETSrelated transcription factor. Only 13 available cases: 9 ANLL and 4 ALL; so far, ANLL cases with a proximal breakpoint in 4q11 or 12 are adult cases (43-77 yrs), and ALL cases are children cases (3-14 yrs); balanced sex ratio. References Prognosis Harada H, Harada Y, Eguchi M, Dohy H, Kamada N. Characterization of acute leukemia with t(4;12). Leuk Lymphoma 1997 Mar;25(1-2):47-53. Adult cases: response to therapy is poor and median survival might be a year. This article should be referenced as such: Huret JL, Lafage-Pochitaloff M. t(4;12)(q11-q21;p13). Atlas Genet Cytogenet Oncol Haematol.1998;2(1):26. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 26 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Leukaemia Section Mini Review t(5;12)(q33;p13) Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France Published in Atlas Database: January 1998 Online version is available at: http://AtlasGeneticsOncology.org/Anomalies/t0512.html DOI: 10.4267/2042/32107 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity Note: this translocation must not be confused with the t(5;12)(q31;p13) found in an ALL cell line with IL3 and ETV6 involvements. t(5;12)(q33;p13) G-banding (left) and R-banding (right) - Courtesy Franck Viguié. Clinics Clinics and pathology Organomegaly in 9 of 12 cases; blood data: median WBC: 40 X 109/l; numerous eosinophils: median 2.8 X 109/l, range 0.8-128 X 109/l, n=9 (normal range is 0.020.45 X 109/l), and, at times, of monocytes; no blast cells. Disease Myeloid lineage. Phenotype / cell stem origin Myeloproliferative/myelodysplastic syndrome (intermediate between CML and CMML) with eosinophilia; appear to be a specific entity. Treatment Hydroxyurea alone or polychemotherapy have been essayed. Epidemiology Prognosis Rarely described; mostly in adult male patients (13 of 14 cases herein reviewed). Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) Yet partly undetermined; median survival < 20 mths (n=11). 27 t(5;12)(q33;p13) Huret JL Description Cytogenetics 5' ETV6 - 3' PDGFRB. Additional anomalies Fusion protein +8. Description N-term HLH domain of ETV6 fused to the transmembrane domain and the Tyr kinase domain of PDGFRb in C-term; the reciprocal transcript is not expressed. Genes involved and Proteins PDGFRB Location: 5q33 References Protein PDGFRB is the receptor for PDGFB (platelet-derived growth factor-b); membrane protein; belongs to the immunoglobulin superfamily. Golub TR, Barker GF, Lovett M, Gilliland DG. Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell 1994 Apr 22;77(2):307-16. ETV6 Wlodarska I, Mecucci C, Marynen P, Guo C, Franckx D, La Starza R, Aventin A, Bosly A, Martelli MF, Cassiman JJ, et al. TEL gene is involved in myelodysplastic syndromes with either the typical t(5;12)(q33;p13) translocation or its variant t(10;12)(q24;p13). Blood 1995 May 15;85(10):2848-52. Location: 12p13 DNA / RNA 9 exons; alternate splicing. Pellier I, Le Moine PJ, Rialland X, François S, Baranger L, Blanchet O, Larget-Piet L, Ifrah N. Myelodysplastic syndrome with t(5;12)(q31;p12-p13) and eosinophilia: a pediatric case with review of literature. J Pediatr Hematol Oncol 1996 Aug;18(3):285-8. (Review). Protein Contains a Helix-Loop-Helix and ETS DNA binding domains; wide expression; nuclear localisation; ETSrelated transcription factor. Results of the chromosomal anomaly This article should be referenced as such: Huret JL. t(5;12)(q33;p13). Atlas Genet Cytogenet Oncol Haematol.1998;2(1):27-28. Hybrid gene Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 28 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Leukaemia Section Mini Review t(6;9)(p23;q34) Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France Published in Atlas Database: January 1998 Online version is available at: http://AtlasGeneticsOncology.org/Anomalies/t0609.html DOI: 10.4267/2042/32108 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Phenotype / cell stem origin Identity M2, M4 ANLL, often preceded by MDS; M1 ANLL or RAEB at times; May be secondary to toxic exposure; A primitive myeloid progenitor is likely to be involved. Epidemiology 1% of ANLL; Found at any age, but median age (25-30 yrs) is less than usual in ANLL; Rare in the elderly; Sex ratio: 1M/1F; Blood data: marked basophilia (> 1% of nucleated cells) in one third to half of the patients. Cytology TdT +; Auer rods. Prognosis Remission difficult to obtain; CR in only half cases; median survival around 1 yr. Cytogenetics Cytogenetics, morphological May be over loocked. Additional anomalies Most often none (80%); recurrent, although rare, additional anomalies are: +8, +13, +21. Variants Three way complex t(6;9;Var) exist. Genes involved and Proteins t(6;9)(p23;q34) G-banding - Courtesy Diane H. Norback, Eric B. Johnson, Sara Morrison-Delap Cytogenetics at the Waisman Center (top and middle top), Jean-Luc Lai (middle below), and Roland Berger (below). DEK Location: 6p23 Protein Clinics and pathology Contains acidic domains and a nuclear localisation signal; DNA binding protein; transcriptional regulation and signal transduction. Disease ANLL and/or MDS. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 29 t(6;9)(p23;q34) Huret JL The translocation t(6;9)(p23;q34) results in the formation of a chimeric fusion gene: DEK (6q23) and CAN (9q34). CAN is a putative oncogene which may be activated by fusion of its 3' end to other genes than DEK. One such recently reported gene is called SET and leads to expression of a SET/CAN fusion RNA. The t(6;9)(p21-22;q34) may be seen in either AML M2 or less frequently in M4 or MDS and acute myelofibrosis often in association with excess basophils. The t(6;9) is reported mostly in young adults. The prognosis of patients carrying the t(6;9) is unfavorable - Courtesy Georges Flandrin, CD-ROM AML/MDS G.Flandrin/ICG. TRIBVN. CAN Detection protocol Location: 9q34 RNA-PCR. Protein Fusion protein Contains dimerization domains → forms homodimers; nuclear membrane localisation; associated with the nuclear pore complex. Description Results of the chromosomal anomaly Expression localisation 165 kDa; N-term with almost the entire DEK protein fused to the C-terminal two-thirds of the CAN protein. Nuclear localisation. References Hybrid gene Pearson MG, Vardiman JW, Le Beau MM, Rowley JD, Schwartz S, Kerman SL, Cohen MM, Fleischman EW, Prigogina EL. Increased numbers of marrow basophils may be associated with a t(6;9) in ANLL. Am J Hematol 1985 Apr;18(4):393-403. Description 5' DEK - 3' CAN on der(6); Head to tail DEK/CAN fusion gene (SET/CAN exceptional); breakpoint clusters in a single intron of 8 kb (ICB9: 'intron containing breakpoint 9') in CAN, and in a single intron (of 12 kb) as well (ICB6) in DEK. von Lindern M, Poustka A, Lerach H, Grosveld G. The (6;9) chromosome translocation, associated with a specific subtype of acute nonlymphocytic leukemia, leads to aberrant transcription of a target gene on 9q34. Mol Cell Biol 1990 Aug;10(8):4016-26. Transcript Soekarman D, von Lindern M, van der Plas DC, Selleri L, Bartram CR, Martiat P, Culligan D, Padua RA, Hasper-Voogt 5.5 kb RNA; no CAN-DEK reciprocal transcript on chromosome 9. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 30 t(6;9)(p23;q34) Huret JL KP, Hagemeijer A, et al. Dek-can rearrangement in translocation (6;9)(p23;q34). Leukemia 1992 Jun;6(6):489-94. Fornerod M, Boer J, van Baal S, Morreau H, Grosveld G. Interaction of cellular proteins with the leukemia specific fusion proteins DEK-CAN and SET-CAN and their normal counterpart, the nucleoporin CAN. Oncogene 1996 Oct 17;13(8):1801-8. von Lindern M, Fornerod M, Soekarman N, van Baal S, Jaeglé M, Hagemeijer A, Bootsma D, Grosveld G. Translocation t(6;9) in acute non-lymphocytic leukaemia results in the formation of a DEK-CAN fusion gene. Baillieres Clin Haematol 1992 Oct;5(4):857-79. (Review). This article should be referenced as such: Huret JL. t(6;9)(p23;q34). Atlas Genet Cytogenet Oncol Haematol.1998;2(1):29-31. Lillington DM, MacCallum PK, Lister TA, Gibbons B. Translocation t(6;9)(p23;q34) in acute myeloid leukemia without myelodysplasia or basophilia: two cases and a review of the literature. Leukemia 1993 Apr;7(4):527-31. (Review). Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 31 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Leukaemia Section Mini Review t(10;11)(p13;q21) Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France Published in Atlas Database: January 1998 Online version is available at: http://AtlasGeneticsOncology.org/Anomalies/t1011bis.html DOI: 10.4267/2042/32109 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity Note: the description of this rare entity is arduous, since cases without molecular studies can be confused with cases of t(10;11)(p12;q23). t(10;11)(p13;q21) R-banding (left) and Fish studies with MLL probe showing a signal on the normal 11 and one on the der(10)(right) and with chromosome 11 paint - Courtesy Pascale Cornillet-Lefebvre and Stéphanie Struski. ascertained by molecular studies are needed before true prognostic ascertainment). Clinics and pathology Disease Cytogenetics A mainly T-cell ALL; at times ANLL and/or ANLL with T-cell markers, or B-cell ALL. Cytogenetics, molecular Phenotype / cell stem origin Investigations are required. A myelomonocytic/T-cell common progenitor may be involved; FAB: L1/L2. Additional anomalies Most often (11/15 cases) present; del(5q), +8, and +19 already recurrent. Epidemiology < 1% of ALL; about 5 % of T-ALL; sex ratio: 9M/5F (from 14 cases herein reviewed). Genes involved and Proteins Clinics Organomegaly; no CNS involvement; blood data: high WBC (range 20-170 X 109/l). AF10 Location: 10p12 Prognosis DNA / RNA Median survival: 22 mths in this review; range: 0-33+ mths, n=11 (but we are to be cautious: cases Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 5' telomeric → 3' centromeric orientation. 32 t(10;11)(p13;q21) Huret JL Contains 3 Zn fingers and a leucine zipper; nuclear localisation; transcription factor. 2- A small 84 amino acids protein with N-term zinc finger from AF10 fused to the very C-term end of CALM. CALM Oncogenesis Location: 11q14-21 It is not known which of the 2 fusion proteins has the critical role. Protein Protein Role in the integration of different signals. References Results of the chromosomal anomaly [No authors listed]. t(10;11)(p13-14;q14-21): a new recurrent translocation in T-cell acute lymphoblastic leukemias. Groupe Français de Cytogénétique Hématologique (GFCH). Genes Chromosomes Cancer 1991 Nov;3(6):411-5. Hybrid gene Secco C, Wiernik PH, Bennett JM, Paietta E. Acute leukemia with t(10;11)(p11-p15;q13-q23). Cancer Genet Cytogenet 1996 Jan;86(1):31-4. Transcript Both 5' CALM - 3' AF10 and 5' AF10 - 3' CALM are expressed. Kobayashi H, Hosoda F, Maseki N, Sakurai M, Imashuku S, Ohki M, Kaneko Y. Hematologic malignancies with the t(10;11)(p13;q21) have the same molecular event and a variety of morphologic or immunologic phenotypes. Genes Chromosomes Cancer 1997 Nov;20(3):253-9. Fusion protein Description 1- A 1595 amino acids protein with N-term and most of CALM (except the last 4 amino acids!) fused to most of AF10 from amino acid 81 (excluding the N-term zinc finger of AF10) C-term. Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) This article should be referenced as such: Huret JL. t(10;11)(p13;q21). Atlas Genet Cytogenet Oncol Haematol.1998;2(1):32-33. 33 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Leukaemia Section Short Communication t(11;14)(q13;q32) in multiple myeloma Jean-Loup Huret, Jean-Luc Laï Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France (JLH); INSERM Unité 524, Institut de Recherche sur le Cancer de Lille, Lille, France (JLL) Published in Atlas Database: January 1998 Online version is available at: http://AtlasGeneticsOncology.org/Anomalies/t1114MM.html DOI: 10.4267/2042/32110 This work is licensed under a Creative Commons Attribution-Non commercial-No Derivative Works 2.0 France Licence. © 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology Clinics and pathology event in MM, lsas it has been found occurring during course of the disease. Disease Cytogenetics, molecular Multiple myeloma (MM) is a malignant plasma cell proliferation. FISH is indicated, as metaphases are arduous to obtain in such a disease implicating mature cells. Phenotype / cell stem origin Additional anomalies Phenotype of mature differentiated B-cell, but also with CD56 expression, which is not found in normal plasma cells. t(11;14) is part of a complex karyotype; accompanied with -13 or del(13q) in 'only' 1/4 of cases while 13/del(13q) is found in about 40% of MM cases with an abnormal karyotype; structural (and variable) anomalies of chromosome 1 are found in 1/3 of cases with t(11;14). Epidemiology Multiple myeloma's annual incidence: 30/106; mean age: 62 yrs; t(11;14) is found in 10-20% of cases of MM with an abnormal karyotype; t(11;14) is not found associated with particular sex or age group; found mostly in stage III MM. Variants Clinics Complex three way translocations t(11;Var;14) have been described. Bone pain; susceptibility to infections; renal failure; neurologic dysfunctions. Genes involved and Proteins Pathology BCL1 MM staging: - Stage I: low tumour cell mass; normal Hb; low serum calcium; no bone lesion; low monoclonal Ig rate; - Stage II: fitting neither stage I nor stage II; - Stage III: high tumour cell mass; low Hb and/or high serum calcium and/or advanced lytic bone lesions and/or high monoclonal Ig rate. Location: 11q13 IgH Location: 14q32 References Feinman R, Sawyer J, Hardin J, Tricot G. Cytogenetics and molecular genetics in multiple myeloma. Hematol Oncol Clin North Am 1997 Feb;11(1):1-25. (Review). Prognosis Evolution: multiple myeloma can evolve towards plasma cell leukaemia; Prognosis (highly variable) is according to the staging and other parameters, of which are now the karyotypic findings. Laï JL, Michaux L, Dastugue N, Vasseur F, Daudignon A, Facon T, Bauters F, Zandecki M. Cytogenetics in multiple myeloma: a multicenter study of 24 patients with t(11;14)(q13;q32) or its variant. Cancer Genet Cytogenet 1998 Jul 15;104(2):133-8. Cytogenetics This article should be referenced as such: Cytogenetics, morphological Huret JL, Laï JL. t(11;14)(q13;q32) in multiple myeloma. Atlas Genet Cytogenet Oncol Haematol.1998;2(1):34. t(11;14) is balanced in most cases; some cases are: -14, +der(14)t(11;14); t(11;14) may well be a secondary Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1) 34 t(11;14)(q13;q32) in multiple myeloma Atlas of Genetics and Cytogenetics in Oncology and Haematology Huret JL, Laï JL OPEN ACCESS JOURNAL AT INIST-CNRS Instructions to Authors Manuscripts submitted to the Atlas must be submitted solely to the Atlas. Iconography is most welcome: there is no space restriction. The Atlas publishes "cards", "deep insights", "case reports", and "educational items". Cards are structured review articles. 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