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Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Leukaemia Section Mini Review t(14;15)(q32;q11-13) Silvia Rasi, Gianluca Gaidano Division of Hematology, Department of Clinical and Experimental Medicine & Center of Biotechnologies for Applied Medical Research, Amedeo Avogadro University of Eastern Piedmont, Via Solaroli 17, 28100 Novara, Italy (SR, GG) Published in Atlas Database: July 2008 Online updated version : http://AtlasGeneticsOncology.org/Anomalies/t1415q32q12ID1349.html DOI: 10.4267/2042/44522 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2009 Atlas of Genetics and Cytogenetics in Oncology and Haematology Clinics and pathology Cytogenetics Disease Additional anomalies Diffuse large B-cell lymphoma (DLBCL). DLBCL is a molecularly heterogeneous type of aggressive lymphoma, accounting for approximately 40% of all Bcell non-Hodgkin lymphomas (NHL) of the Western world. Translocations involving the chromosomal region 15q11-13 also have been identified in nonlymphoid tumors. DLBCL is a heterogeneous disease with respect to karyotypic abnormalities. t(14;15)(q32;q11-13) is a rare chromosomal translocation restricted to 4-5% DLBCL. The most frequent cytogenetic abnormalities detected in DLBCL involve BCL6 t(3;V)(q27;V), BCL2 t(14;18)(q32;q21), and myc t(8;14)(q24;q32), and occur in 25%, 20% and 10% of DLBCL, respectively. Phenotype/cell stem origin Variants B-cell. The chromosomal translocation t(14;15)(q32;q11-13) can activate BCL8 gene expression in lymphoid tissues, whereas BCL8 expression is not normally found in hematopoietic tissues. In addition to IGHV gene translocation, other translocations of the chromosomal region 15q11-13 involve additional chromosomal sites, including 22q11 (IGLV), 9p13, 1p32, 7p13, 12q24, and 15q22. Genes involved and proteins Epidemiology IgH Translocations affecting 15q11-q13 and various chromosomal partners occur in about 3-4% of DLBCL. Location 14q32 DNA/RNA IgH gene is composed of V (variable), D (diversity), J (joining), and C (constant) segments. During B cell development, a recombination event at the DNA level creates a rearranged IGHV-D-J gene. Protein Proteins encoded by the IgH gene are the immunoglobulin heavy chains. Clinics At present, it is not not yet clear whether chromosomal translocation t(14;15) identifies a homogeneous. Pathology Clinico-pathologic subtype of DLBCL. Prognosis The effect of BCL8 expression on the prognosis of patients has yet to be investigated. Atlas Genet Cytogenet Oncol Haematol. 2009; 13(7) 513 t(14;15)(q32;q11-13) Rasi S, Gaidano G BCL8 Fusion protein Location 15q11-q13 DNA/RNA 3 exons. The 5' part of exon 1 and the 3' part of exon 3 are non coding. Two alternative transcripts: a major transcript of 2.6 kb, and a less expressed transcript of 4.5 kb, due to differential polyadenylation. Protein 100 amino acids, predicted molecular weight of 19 kDa; predicted: similar to protein neurobeachin (Lysosomal trafficking regulator 2). Truncated polypeptides with uncertain function are also produced. Description The chromosomal translocation does not lead to the formation of a fusion protein. Oncogenesis t(14;15)(q32;q11-13) causes activation of the BCL8 proto-oncogene by deregulated expression of BCL8. This chromosomal translocation may contribuite to lymphomagenesis by alterated expression level of BCL8. References Dyomin VG, Rao PH, Dalla-Favera R, Chaganti RS. BCL8, a novel gene involved in translocations affecting band 15q11-13 in diffuse large-cell lymphoma. Proc Natl Acad Sci U S A. 1997 May 27;94(11):5728-32 Result of the chromosomal anomaly Macintyre E, Willerford D, Morris SW. Non-Hodgkin's Lymphoma: Molecular Features of B Cell Lymphoma. Hematology Am Soc Hematol Educ Program. 2000;:180-204 Hybrid gene Description The translocation t(14;15)(q32;q11-13) leaves the coding region of BCL8 gene intact, and does not lead to the formation of a hybrid gene. BCL8 is adjacent to the chromosomal breakpoint, that is located upstream of a rearranged VH segment. BCL8 is a part of a large duplicated region within 15q11 containing several pseudogenes, including orphan IGH copies of V and D segments and it's possible that this V/D segments can rearrange with D/J segments on chromosome 14. Atlas Genet Cytogenet Oncol Haematol. 2009; 13(7) Dyomin VG, Chaganti SR, Dyomina K, Palanisamy N, Murty VV, Dalla-Favera R, Chaganti RS. BCL8 is a novel, evolutionarily conserved human gene family encoding proteins with presumptive protein kinase A anchoring function. Genomics. 2002 Aug;80(2):158-65 Rossi D, Gaidano G. Molecular heterogeneity of diffuse large B-cell lymphoma: implications for disease management and prognosis. Hematology. 2002 Aug;7(4):239-52 This article should be referenced as such: Rasi S, Gaidano G. t(14;15)(q32;q11-13). Atlas Genet Cytogenet Oncol Haematol. 2009; 13(7):513-514. 514