| Written | 2008-07 | Silvia Rasi, Gianluca Gaidano |
| Division of Hematology, Department of Clinical, Experimental Medicine & Center of Biotechnologies for Applied Medical Research, Amedeo Avogadro University of Eastern Piedmont, Via Solaroli 17, 28100 Novara, Italy |
| Identity |
| ICD-Topo | C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS |
| Atlas_Id | 1349 |
| Clinics and Pathology |
| Disease | Diffuse large B-cell lymphoma (DLBCL). DLBCL is a molecularly heterogeneous type of aggressive lymphoma, accounting for approximately 40% of all B-cell non-Hodgkin lymphomas (NHL) of the Western world. Translocations involving the chromosomal region 15q11-13 also have been identified in nonlymphoid tumors. |
| Phenotype / cell stem origin | 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. |
| Epidemiology | Translocations affecting 15q11-q13 and various chromosomal partners occur in about 3-4% of DLBCL. |
| Clinics | At present, it is not not yet clear whether chromosomal translocation (t14;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. |
| Cytogenetics |
| Additional anomalies | 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. |
| Variants | 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 |
| Gene Name | IGH (Immunoglobulin Heavy) |
| Location | 14q32.33 |
| 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. |
| Gene Name | NBEAP1 (B-cell CLL/lymphoma 8) |
| Location | 15q11.2 |
| 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 2.6Kb, and a less expressed transcript of 4.5Kb, 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. |
| Result of the chromosomal anomaly |
| 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. |
| 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. |
| Bibliography |
| BCL8 is a novel, evolutionarily conserved human gene family encoding proteins with presumptive protein kinase A anchoring function. |
| Dyomin VG, Chaganti SR, Dyomina K, Palanisamy N, Murty VVVS, Dalla Favera R, Chaganti RSK. |
| Genomics. 2002; 80(2): 158-165. |
| PMID 12160729 |
| Bcl8, a novel gene involved in translocations affecting band 15q11-13 in diffuse large-cell lymphoma. |
| Dyomin VG, Rao PH, Dalla Favera R, Chaganti RSK. |
| Proc Natl Acad Sci USA. 1997; 94: 5728-5732. |
| PMID 9159141 |
| Non-Hodgkin's Lymphoma: Molecular Features of B Cell Lymphoma. |
| Macintyre E, Willerford D, Morrsi SW. |
| Hematology Am Soc Hematol Educ Program. 2000; 180-204. |
| PMID 11701542 |
| Molecular heterogeneity of diffuse large B-cell lymphoma: implications for disease management and prognosis. |
| Rossi D, Gaidano G. |
| Hematology. 2002; 7(4): 239-252. |
| PMID 14972786 |
| Citation |
| This paper 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. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/t1415q32q12ID1349.html |
| Other genes implicated (Data extracted from papers in the Atlas) [ 1 ] |
| Genes | NBEAP1 |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(14;15)(q32;q11) IGH/NBEAP1 | |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| All articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Mon Sep 18 17:20:14 CEST 2017 |
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