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Translocations t(11;18)(q21;q21) and t(14;18)(q32;q21) are the main chromosomal abnormalities involving MLT/MALT1 in MALT lymphomas

Abstract

The recently discovered MLT/MALT1 gene is fused with the API2 gene in the t(11;18)(q21;q21), which characterizes about one-third of MALT lymphomas. In order to screen for variant translocations and amplifications of MLT/MALT1, we have developed a novel, undirected two-color interphase fluorescence in situ hybridization (FISH) assay with two PAC clones flanking MLT/MALT1. This assay was applied to 108 marginal zone B-cell lymphomas (MZBCLs), including 72 extranodal MALT lymphomas, 17 nodal, and 19 splenic MZBCL. In 19 MALT lymphomas (26%), but in none of the nodal or splenic MZBCL, separated hybridization signals of the MLT/MALT1 flanking probes, were found. Further FISH analyses showed that 12 of these 19 cases displayed the classical t(11;18) and the remaining seven cases revealed the novel t(14;18)(q32;q21), involving the MLT/MALT1 and IGH genes. The frequency at which these translocations occurred varied significantly with the primary location of disease. The t(11;18) was mainly detected in gastrointestinal MALT lymphomas, whereas the t(14;18) occurred in MALT lymphomas of the parotid gland and the conjunctiva. Amplification of MLT/MALT1 was not observed in any of the lymphomas analyzed. We conclude that the translocations t(11;18)(q21;q21) and t(14;18)(q21;q32) represent the main structural aberrations involving MLT/MALT1 in MALT lymphomas, whereas true amplifications of MLT/MALT1 occur rarely in MZBCL.

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References

  1. Auer IA, Gascoyne RD, Connors JM, Cotter FE, Greiner TV, Sanger WG et al. t(11;18)(q21;q21) is the most common translocation in MALT lymphomas. Ann Oncol 1997; 8: 979–985.

    Article  CAS  Google Scholar 

  2. Ott G, Katzenberger T, Greiner A, Kalla J, Rosenwald A, Heinrich U et al. The t(11;18)(q21;q21) chromosome translocation is a frequent and specific aberration in low-grade but not high-grade malignant non-Hodgkin's lymphomas of the mucosa-associated lymphoid tissue (MALT-)type. Cancer Res 1997; 57: 3944–3948.

    CAS  Google Scholar 

  3. Dierlamm J, Baens M, Wlodarska I, Stefanova-Ouzounova M, Hernandez JM, Hossfeld DK et al. The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with MALT lymphomas. Blood 1999; 93: 3601–3609.

    CAS  Google Scholar 

  4. Rosenwald A, Ott G, Stilgenbauer S, Kalla J, Bredt M, Katzenberger T et al. Exclusive detection of the t(11;18)(q21;q21) in extranodal marginal zone B cell lymphomas (MZBL) of MALT type in contrast to other MZBL and extranodal large B cell lymphomas. Am J Pathol 1999; 155: 17–1821.

    Article  Google Scholar 

  5. Dierlamm J, Baens M, Stefanova-Ouzounova M, Hinz K, Wlodarska I, Steyls A et al. Detection of t(11;18)(q21;q21) by interphase fluorescence in situ hybridization using API2 and MLT specific probes. Blood 2000; 96: 2215–2218.

    CAS  PubMed  Google Scholar 

  6. Dierlamm J . Genetic abnormalities in marginal zone B-cell lymphoma. Haematologica 2003; 88: 8–12.

    PubMed  Google Scholar 

  7. Akagi T, Motegi M, Tamura A, Suzuki R, Hosokawa Y, Suzuki H et al. A novel gene, MALT1 at 18q21, is involved in t(11;18)(q21;q21) found in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue. Oncogene 1999; 18: 5785–5794.

    Article  CAS  Google Scholar 

  8. Morgan JA, Yin Y, Borowsky AD, Kuo F, Nourmand N, Koontz JI et al. Breakpoints of the t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma lie within or near the previously undescribed gene MALT1 in chromosome 18. Cancer Res 1999; 59: 6205–6213.

    CAS  Google Scholar 

  9. Baens M, Steyls A, Dierlamm J, De Wolf-Peeters C, Marynen P . Structure of the MLT gene and molecular characterization of the genomic breakpoint junctions in the t(11;18)(q21;q21) of marginal zone B-cell lymphomas of MALT type. Genes Chromosomes Cancer 2000; 29: 281–291.

    Article  CAS  Google Scholar 

  10. Kalla J, Stilgenbauer S, Schaffner C, Wolf S, Ott G, Greiner A et al. Heterogeneity of the API2-MALT1 gene rearrangement in MALT-type lymphoma. Leukemia 2000; 14: 1967–1974.

    Article  CAS  Google Scholar 

  11. Remstein ED, James CD, Kurtin PJ . Incidence and subtype specificity of API2-MALT1 fusion translocations in extranodal, nodal, and splenic marginal zone lymphomas. Am J Pathol 2000; 156: 1183–1188.

    Article  CAS  Google Scholar 

  12. Uren AG, O'Rourke K, Aravind L, Pisabarro MT, Seshagiri S, Koonin EV et al. Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma. Mol Cell 2000; 6: 961–967.

    CAS  PubMed  Google Scholar 

  13. Lucas PC, Yonezumi M, Inohara N, McAllister-Lucas LM, Abazeed ME, Chen FF et al. Bcl10 and MALT1, independent targets of chromosomal translocation in MALT lymphoma, cooperate in a novel NF-κB signaling pathway. J Biol Chem 2001; 276: 19012–19019.

    Article  CAS  Google Scholar 

  14. Ye H, Liu H, Attygalle A, Wotherspoon AC, Nicholson AG, Charlotte F et al. Variable frequencies of t(11;18)(q21;q21) in MALT lymphomas of different sites: significant association with CagA strains of H. pylori in gastric MALT lymphoma. Blood 2003; 102: 1.012–1.018.

    Article  Google Scholar 

  15. Liu H, Ye H, Ruskone-Fourmestraux A, De Jong D, Pileri S, Thiede C . t(11;18) is a marker for all stage gastric MALT lymphomas that will not respond to H. pylori eradication. Gastroenterology 2002; 122: 1286–1294.

    Article  CAS  Google Scholar 

  16. Ye H, Liu H, Radere M, Chott A, Ruskone-Fourmestraux A, Wotherspoon A et al. High incidence of t(11;18)(q21;q21) in Helicobacter pylori-negative gastric MALT lymphomas. Blood 2003; 101: 2547–2550.

    Article  CAS  Google Scholar 

  17. Sanchez-Izquierdo D, Buchonnet G, Siebert R, Gascoyne RD, Climent J, Karran L et al. MLT/MALT1 is deregulated by both chromosomal translocation and amplification in B-cell non-Hodgkin lymphoma. Blood 2003; 101: 4539–4546.

    Article  CAS  Google Scholar 

  18. Streubel B, Lamprecht A, Dierlamm J, Cerroni L, Stolte M, Ott G et al. T(14;18)(q32;q21) involving IGH and MLT/MALT1 is a frequent chromosomal aberration in MALT lymphoma. Blood 2003; 101: 2335–2339.

    Article  CAS  Google Scholar 

  19. Joos S, Haluska FG, Falk MH, Henglein B, Hameister H, Croce CM et al. Mapping chromosomal breakpoints of Burkitt's (8;14) translocations far upstream of c-myc. Cancer Res 1992; 52: 6547–6552.

    CAS  PubMed  Google Scholar 

  20. Kallioniemi OP, Kallioniemi A, Kuriso W, Thor A, Chen LC, Smith HS et al. ERBB2 amplification in breast cancer analyzed by fluorescence in situ hybridization. Proc Natl Acad Sci USA 1992; 89: 5321–5325.

    Article  CAS  Google Scholar 

  21. Visakorpi T, Hyytinen E, Koivisto P, Tanner M, Keinänen R, Palmberg C et al. In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat Genet 1995; 9: 401–406.

    Article  CAS  Google Scholar 

  22. Silverman GA, Green ED, Young RL, Jockel JI, Domer PH, Korsmeyer SJ . Meiotic recombination between yeast artificial chromosomes yields a single clone containing the entire BCL2 protooncogene. Proc Natl Acad Sci USA 1990; 87: 9913–9917.

    Article  CAS  Google Scholar 

  23. Dierlamm J, Wlodarska I, Michaux L, La Starza R, Zeller W, Meccuci C et al. Successful use of the same slide for consecutive fluorescence in situ hybridization experiments. Genes Chromosomes Cancer 1996; 16: 261–264.

    Article  CAS  Google Scholar 

  24. Motegi M, Yonezumi M, Suzuki H, Suzuki R, Hosakawa Y, Hosaka S et al. API2-MALT1 chimeric transcripts involved in mucosa-associated lymphoid tissue type lymphoma predict heterogeneous products. Am J Pathol 2000; 156: 807–812.

    Article  CAS  Google Scholar 

  25. Dierlamm J, Pittaluga S, Wlodarska I, Stul M, Thomas J, Boogaerts M et al. Marginal zone B-cell lymphomas of different sites share similar cytogenetic and morphologic features. Blood 1996; 87: 299–307.

    CAS  PubMed  Google Scholar 

  26. Dierlamm J, Rosenberg C, Stul M, Pittaluga S, Wlodarska I, Michaux L et al. Characteristic pattern of chromosomal gains and losses in marginal zone B cell lymphoma detected by comparative genomic hybridization. Leukemia 1997; 11: 747–758.

    Article  CAS  Google Scholar 

  27. Wotherspoon AC, Finn TM, Isaacson PG . Trisomy 3 in low-grade B-cell lymphomas of the mucosa associated lymphoid tissue. Blood 1995; 85: 2000–2004.

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by Grant 70-3019Di3 from the Deutsche Krebshilfe/Dr Mildred Scheel Stiftung für Krebsforschung.

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Penas, E., Hinz, K., Röser, K. et al. Translocations t(11;18)(q21;q21) and t(14;18)(q32;q21) are the main chromosomal abnormalities involving MLT/MALT1 in MALT lymphomas. Leukemia 17, 2225–2229 (2003). https://doi.org/10.1038/sj.leu.2403122

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