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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
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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
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Atlas Genet Cytogenet Oncol Haematol. 1998; 2(1)
Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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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
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in Oncology and Haematology
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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
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in Oncology and Haematology
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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)
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in Oncology and Haematology
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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
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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
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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
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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
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in Oncology and Haematology
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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
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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
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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
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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
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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
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in Oncology and Haematology
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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
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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
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