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Frequent allelic loss of the BCL10 gene in lymphomas with the t(11;14)(q13;q32)

Leukemia volume 15, pages 474–475 (2001)Cite this article

The translocation t(11;14)(q13;q32) is the cytogenetic hallmark of mantle cell lymphomas (MCL), in which it can be detected in over 80% of cases. Additionally, this translocation has been observed in subsets of other B-lymphocytic neoplasms.1 At the molecular level, the t(11;14) juxtaposes the BCL1-locus in chromosome band 11q13 next to the immunoglobulin heavy chain (IgH) locus in chromosome band 14q32, resulting in overexpression of cyclin D1 (CCND1). Cyclin D1 protein plays a crucial role in cell cycle progression by promoting the G1-S phase transition. Though overexpression of CCND1 due to the t(11;14) is regarded as the primary event in the pathogenesis of mantle cell lymphomas, experimental data from transgenic mice suggest that cyclin D1 has minimal oncogenic potential, being insufficient to induce tumorigenicity by itself. Thus, the acquisition of secondary chromosomal aberrations appears to be crucial for the malignant transformation and clonal progression of CCND1-overexpressing lymphocytes. By karyotyping, such secondary chromosomal changes can be observed in more than 80% of B cell malignancies with t(11;14). Among the most frequently recurring secondary changes in these neoplasms are deletions in the short arm of chromosome 1 (1p). The common region of loss in cytogenetic as well as CGH studies encompasses 1p22, suggesting the existence of a tumor suppressor gene involved in the pathogenesis of t(11;14)-positive B cell in this chromosomal region.2 3 Chromosome region 1p22 harbors the BCL10 gene, which we and others recently cloned from the translocation t(1;14)(p22;q32) recurrent in mucosa-associated lymphoid tissue (MALT) lymphomas.4 5 The BCL10 gene encodes a caspase recruitment domain (CARD)-containing apoptosis signaling protein that is capable of promoting apoptosis and suppressing in vitro transformation of rat embryonic fibroblasts by synergistic oncogenes. BCL10 cDNAs from t(1;14)-positive MALT tumors contain a striking variety of mutations that abrogate the pro-apoptotic function of the normal protein.4 5 These data suggest that wild-type BCL10 may act as a tumor suppressor.

In order to determine whether the second allele of the BCL10 gene is also inactivated, seven primary cases with FISH-proven BCL10 deletions and at least 45% aberrant cells, as well as the cell line Granta 519, were subjected to genomic mutation screening of the complete BCL10 open reading frame by direct SSCP and sequencing analyses (primers were derived from the genomic BCL10 sequence, Acc. No. AF097732, sequences available upon request). Besides the mentioned polymorphisms no clonal mutations of the second allele of BCL10 were detected in any of the eight lymphomas.

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References

  1. Raffeld M, Jaffe ES . bcl-1, t(11;14), and mantle cell-derived lymphomas Blood 1991 78: 259–263

    CAS  PubMed  Google Scholar 

  2. Wlodarska I, Pittaluga S, Hagemeijer A, Wolf-Peeters C, Van Den Berghe H . Secondary chromosome changes in mantle cell lymphoma Haematologica 1999 84: 594–599

    CAS  PubMed  Google Scholar 

  3. Bea S, Ribas M, Hernandez JM, Bosch F, Pinyol M, Hernandez L, Garcia JL, Flores T, Gonzalez M, Lopez-Guillermo A, Piris MA, Cardesa A, Montserrat E, Miro R, Campo E . Increased number of chromosomal imbalances and high-level DNA amplifications in mantle cell lymphoma are associated with blastoid variants Blood 1999 93: 4365–4374

    CAS  PubMed  Google Scholar 

  4. Zhang Q, Siebert R, Yan M, Hinzmann B, Cui X, Xue L, Rakestraw KM, Naeve CW, Beckmann G, Weisenburger DD, Sanger WG, Nowotny H, Vesely M, Callet-Bauchu E, Salles G, Dixit VM, Rosenthal A, Schlegelberger B, Morris SW . Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32) Nat Genet 1999 22: 63–68

    Article  CAS  Google Scholar 

  5. Willis TG, Jadayel DM, Du MQ, Peng H, Perry AR, Abdul-Rauf M, Price H, Karran L, Majekodunmi O, Wlodarska I, Pan L, Crook T, Hamoudi R, Isaacson PG, Dyer MJ . Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types Cell 1999 96: 35–45

    Article  CAS  Google Scholar 

  6. Bullinger L, Leupolt E, Schaffner C, Mertens D, Bentz M, Lichter P, Döhner H, Stilgenbauer S . BCL10 is not the gene inactivated by mutation in the 1p22 deletion region in mantle cell lymphoma Leukemia 2000 14: 1490–1492

    Article  CAS  Google Scholar 

  7. Steinemann D, Siebert R, Martin-Subero I, Harder S, Kettwig G, Gesk S, Hinzmann B, Rosenthal A, Morris SW, Grote W, Schlegelberger B . Frequent allelic loss of the BCL 10 gene in lymphomas with the translocation t(11;14)(q13;q32) Eur J Hum Genet 2000 8: 505

    Google Scholar 

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Authors and Affiliations

  1. Institute of Human Genetics, University of Kiel, Kiel, Germany

    D Steinemann, R Siebert, S Harder, I Martin-Subero, G Kettwig, S Gesk, W Grote & B Schlegelberger

  2. metaGen Gesellschaft für Genomforschung mbH, Berlin, Germany

    B Hinzmann & A Rosenthal

  3. Department of Hematopathology, University of Kiel, Kiel, Germany

    M Tiemann

  4. Department of Pathology, University of Lübeck, Lübeck, Germany

    H Merz

  5. Departments of Pathology and Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN, USA

    SW Morris

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  1. D Steinemann
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Steinemann, D., Siebert, R., Harder, S. et al. Frequent allelic loss of the BCL10 gene in lymphomas with the t(11;14)(q13;q32). Leukemia 15, 474–475 (2001). https://doi.org/10.1038/sj.leu.2402037

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