Atlas of Genetics and Cytogenetics in Oncology and Haematology
t(9;14)(p13;q32)
| Identity |
 | |
| t(9;14)(p13;q32) (G- banding) top left: Courtesy Bruce Poppe, Pascale De Paepe, Frank Speleman, top right: Courtesy Jean-Luc Lai, bottom: Diane H. Norback, Eric B. Johnson, Sara Morrison-Delap UW Cytogenetic Services . | |
| Clinics and Pathology |
| Disease | Rare recurrent chromosomal aberration, exclusively detected in B-cell lymphoproliferative disorders. |
| Phenotype / cell stem origin | B lymphocyte. |
| Epidemiology | Originally reported to be associated with a low-grade mature B-cell phenotype with plasmacytoid differentiation such as lymphoplasmacytic lymphoma, multiple myeloma/ plasma cell leukemia and chronic lymphocytic leukemia. However, the relatively frequent occurrence in diffuse large B-cell lymphoma, with or without a preceding faze of a low-grade lymphoma, suggests that this chromosomal aberration has a much wider clinical spectrum or is associated with disease progression. In addition, the t(9;14)(p13;q32) has been described occasionally in follicular lymphoma, mantle cell lymphoma and splenic marginal zone lymphoma. |
| Prognosis | No prognostic relevance has been attributed to the presence of the t(9;14)(p13;q32). |
| Cytogenetics |
| Cytogenetics Morphological | The t(9;14)(p13;q32) is readily recognisable with G- as well as R-banding. The presence of complex chromosomal aberrations, however, can mask the presence of this rearrangement. |
 | |
| Dual and triple colour hybridisations demonstrating the presence of a t(9;14)(p13;q32) resulting in PAX5/IGH rearrangement. A,B: partial metaphase and interphase nucleus cohybridized with PAX5 locus specific probes (yellow) and dual colour interphaze cytogenetics using IgH flanking probes (red) and PAX5 locus specific probes. | |
| Additional anomalies | No recurrent additional aberrations have been described. However, the majority of t(9;14)(p13;q32) have been reported in addition to complex chromosomal aberrations. |
| Variants | In addition to the t(9;14)(p13;q32), other translocations presumably involving the immunoglobulin light chain genes and PAX5 have been reported, such as the t(2;9)(p12;p13) and the t(9;22)(p13;q11). |
| Genes involved and Proteins |
| Gene Name | IgH |
| Location | 14q32 |
| Gene Name | PAX5 |
| Location | 9p13 |
| Dna / Rna | The PAX5 coding region extends over a genomic interval of approximately 200kb and comprises 10 exons. Two alternative transcripts have been identified, originating from alternative promotor usage, containing exon 1A or 1B. Full length mRNA is 3650bp. |
| Protein | PAX5 belongs to the paired box family of transcription factors, involved in a multitude of developmental processes. PAX5 was originally identified as a B-cell specific transcription factor (hence its original name, BSAP). Recently it has been shown that PAX5 expression is continuously required in B cell lineage commitment during early B cell development. |
| Result of the chromosomal anomaly |
| Description | Translocation of the entire PAX5 gene to chromosome 14. The breakpoints at 9p13 are heterogeneous and can reside up to 200kb upstream (i.e. centromeric) of PAX5. |
| Detection | The variability of the chromosomal breakpoints at 9p13 as well 14q32 precludes genomic PCR approaches for detection of IgH PAX5 juxtaposition. In addition, the expression pattern of PAX5 hampers RT-PCR methods for demonstrating elevated PAX5 expression in B-cell proliferations with suspected or proven PAX5 rearrangement. Currently, the only methods for detecting IgH PAX5 juxtaposition reliably include conventional and molecular cytogenetics. |
| Description | In analogy to other 14q32 rearrangements, no fusion gene is created by the translocation. Rather, the genomic rearrangement leads to forced PAX5 expression. |
| Oncogenesis | In contrast to the novel insights in the role of PAX5 in B-cell lineage commitment, little is know on the role of PAX5 in the malignant transformation of B cells. The recent demonstration of PAX5 hypermutation in diffuse large-cell lymphomas, in addition to PAX5 overexpression associated with the t(9;14), suggest that PAX5 acts as a dominant oncogene. |
| External links |
| Other database | t(9;14)(p13;q32) | Mitelman database (CGAP - NCBI) |
| Bibliography |
| A novel B-cell lineage-specific transcription factor present at early but not late stages of differentiation. |
| Barberis A, Widenhorn K, Vitelli L, Busslinger M |
| Genes & development. 1990 ; 4 (5) : 849-859. |
| PMID 2116362 |
| t(9;14)(p13;q32) denotes a subset of low-grade non-Hodgkin's lymphoma with plasmacytoid differentiation. |
| Offit K, Parsa NZ, Filippa D, Jhanwar SC, Chaganti RS |
| Blood. 1992 ; 80 (10) : 2594-2599. |
| PMID 1384792 |
| Deregulation of PAX-5 by translocation of the Emu enhancer of the IgH locus adjacent to two alternative PAX-5 promoters in a diffuse large-cell lymphoma. |
| Busslinger M, Klix N, Pfeffer P, Graninger PG, Kozmik Z |
| Proceedings of the National Academy of Sciences of the United States of America. 1996 ; 93 (12) : 6129-6134. |
| PMID 8650231 |
| The t(9;14)(p13;q32) chromosomal translocation associated with lymphoplasmacytoid lymphoma involves the PAX-5 gene. |
| Iida S, Rao PH, Nallasivam P, Hibshoosh H, Butler M, Louie DC, Dyomin V, Ohno H, Chaganti RS, Dalla-Favera R |
| Blood. 1996 ; 88 (11) : 4110-4117. |
| PMID 8943844 |
| High incidence of cryptic translocations involving the Ig heavy chain gene in multiple myeloma, as shown by fluorescence in situ hybridization. |
| Avet-Loiseau H, Brigaudeau C, Morineau N, Talmant P, LaˆØ JL, Daviet A, Li JY, Praloran V, Rapp MJ, Harousseau JL, Facon T, Bataille R |
| Genes, chromosomes & cancer. 1999 ; 24 (1) : 9-15. |
| PMID 9892103 |
| Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. |
| Nutt SL, Heavey B, Rolink AG, Busslinger M |
| Nature. 1999 ; 401 (6753) : 556-562. |
| PMID 10524622 |
| The t(9;14)(p13;q32) translocation in B-cell non-Hodgkin's lymphoma. |
| Ohno H, Ueda C, Akasaka T |
| Leukemia & lymphoma. 2000 ; 36 (5-6) : 435-445. |
| PMID 10784387 |
| Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. |
| Pasqualucci L, Neumeister P, Goossens T, Nanjangud G, Chaganti RS, Kˆºppers R, Dalla-Favera R |
| Nature. 2001 ; 412 (6844) : 341-346. |
| PMID 11460166 |
| Detection of illegitimate rearrangement within the immunoglobulin locus on 14q32.3 in B-cell malignancies using end-sequenced probes. |
| Poulsen TS, Silahtaroglu AN, Gisselˆ½ CG, Gaarsdal E, Rasmussen T, Tommerup N, Johnsen HE |
| Genes, chromosomes & cancer. 2001 ; 32 (3) : 265-274. |
| PMID 11579466 |
| Reversion of B cell commitment upon loss of Pax5 expression. |
| Mikkola I, Heavey B, Horcher M, Busslinger M |
| Science (New York, N.Y.). 2002 ; 297 (5578) : 110-113. |
| PMID 12098702 |
| Contributor(s) |
| Written | 10-2002 | Bruce Poppe, Pascale De Paepe, Frank Speleman |
| Center for Medical Genetics, Ghent University Hospital MRB, De Pintelaan 185, 9000 Ghent, Belgium |
| Citation |
| This paper should be referenced as such : |
| Poppe B, De Paepe P, Speleman F . t(9;14)(p13;q32). Atlas Genet Cytogenet Oncol Haematol. October 2002 . URL : http://AtlasGeneticsOncology.org/Anomalies/t0914p13q32ID2018.html |
This paper is referenced by INIST as such : |
| http://documents.irevues.inist.fr/bitstream/2042/37934/1/10-2002-t0914p13q32ID2018.pdf [ Bibliographic record ] |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Sat Mar 9 12:37:37 CET 2013 |
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