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Lymphoma

Heterogeneous copy numbers of API2-MALT1 chimeric transcripts in mucosa-associated lymphoid tissue lymphoma

Leukemia volume 17, pages 2508–2512 (2003)Cite this article

Abstract

T(11;18)(q21;q21) results in a chimeric transcript between API2 at 11q21 and MALT1 at 18q21 and is a characteristic chromosomal aberration of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). API2-MALT1 chimeric transcripts are present in approximately one-third of all cases of MALT lymphoma. MALT lymphoma is also known to have variations in histological features and tumor cell proportions. Real-time polymerase chain reaction (PCR) was used to examine number of API2-MALT1 copies in clinical samples for further investigation of the pathophysiology of MALT lymphoma. A total of 13 samples of MALT lymphoma contained API2-MALT1 transcripts from 1.7 × 10−2 to 1.0 copies/β-actin copy. These findings were compared to the proportions of tumor cells in genomic VDJ PCR products determined by Southern blotting. Tumor cell ratios varied widely among the patients' samples, and no significant correlation was found between transcript copy number and tumor cell ratio. These results suggest that copy numbers of API2-MALT1 do not reflect tumor cell proportions, and that the number of copies of API2-MALT1 in a tumor cell is different for each clinical sample.

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References

  1. A clinical evaluation of the International lymphoma Study Group classification of Non-Hodgkin's Lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood 1997; 89: 3909–3918.

  2. Horsman D, Gascoyne R, Klasa R, Coupland R . t(11;18)(q21;q21.): a recurring translocation in lymphomas of mucosa-associated lymphoid tissue (MALT)? Genes Chromosomes Cancer 1992; 4: 183–187.

    Article  CAS  Google Scholar 

  3. Auer IA, Gascoyne RD, Conners JM, Cotter FE, Greiner TC, Sanger WG, Horsman DE . t(11;18)(q21;q21) is the most common translocation in MALT lymphomas. Ann Oncol 1997; 8: 979–985.

    Article  CAS  Google Scholar 

  4. Akagi T, Motegi T, 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 

  5. 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 mucosa-associated lymphoid tissue lymphomas. Blood 1999; 93: 3601–3609.

    CAS  PubMed  Google Scholar 

  6. Stoffel A, Rao PH, Louie DC, Krauter K, Liebowitz DN, Koeppen H et al. Chromosome 18 breakpoint in t(11;18)(q21;q21) translocation associated with MALT lymphoma is proximal to BCL2 and distal to DCC. Genes Chromosomes Cancer 1999; 24: 156–159.

    Article  CAS  Google Scholar 

  7. 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 

  8. Motegi M, Yonezumi M, Suzuki H, Suzuki R, Hosokawa 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 

  9. Yonezumi M, Suzuki R, Suzuki H, Yoshino T, Oshima K, Hosokawa Y et al. Detection of AP12-MALT1 chimaeric gene in extranodal and nodal marginal zone B-cell lymphoma by reverse transcription polymerase chain reaction (PCR) and genomic long and accurate PCR analyses. Br J Haematol 2001; 115: 588–594.

    Article  CAS  Google Scholar 

  10. Maes B, Baens M, Marynen P, De Wolf-Peeters C . The product of the t(11;18), an API2-MLT fusion, is an almost exclusive finding in marginal zone cell lymphoma of extranodal MALT-type. Ann Oncol 2000; 11: 521–526.

    Article  CAS  Google Scholar 

  11. 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: 1817–1821.

    Article  CAS  Google Scholar 

  12. 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 

  13. Isaacson P, Wright DH . Extranodal malignant lymphoma arising from mucosa-associated lymphoid tissue. Cancer 1984; 53: 2515–2524.

    Article  CAS  Google Scholar 

  14. Harris NL, Isaacson PG . What are the criteria for distinguishing MALT from non-MALT lymphoma at extranodal sites? Am J Clin Pathol 1999; 111: S126–S132.

    CAS  PubMed  Google Scholar 

  15. Isaacson PG, Berger F, Muller-Hermelink HK, Nathwani BN, Piris MA, Swerdlow SH et al. Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). In: Jaffe ES, Harris NL, Stein H, Vardiman JW (eds) World Health Organization Classification of Tumors. Pathology and Genetics of Tumors of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press, 2001, pp. 157–160.

    Google Scholar 

  16. Wotherspoon AC, Ortiz-Hidalgo C, Falzon MR, Isaacson PG . Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. Lancet 1991; 338: 1175–1176.

    Article  CAS  Google Scholar 

  17. Holm LE, Blomgren H, Lowhagen T . Cancer risks in patients with chronic lymphocytic thyroiditis. N Engl J Med 1985; 312: 601–604.

    Article  CAS  Google Scholar 

  18. Kassan SS, Thomas TL, Moutsopoulos HM, Hoover R, Kimberly RP, Budman DR et al. Increased risk of lymphoma in Sicca syndrome. Ann Intern Med 1978; 89: 888–892.

    Article  CAS  Google Scholar 

  19. Suzuki R, Yamamoto K, Seto M, Kagami Y, Ogura M, Yatabe Y et al. CD7+ and CD56+ myeloid/natural killer cell precursor acute leukemia: a distinct hematolymphoid disease entity. Blood 1997; 90: 2417–2428.

    CAS  PubMed  Google Scholar 

  20. Leclercm GJ, Leclerc GM, Barredo JC . Real-time RT-PCR analysis of mRNA decay: half-life of Beta-actin mRNA in human leukemia CCRF-CEM and Nalm-6 cell lines. Cancer Cell Int 2002; 2: 1–5.

    Article  Google Scholar 

  21. Kume M, Suzuki R, Yatabe Y, Kagami Y, Miura I, Miura AB et al. Somatic hypermutations in the VH segment of immunoglobulin genes of CD5-positive diffuse large B-cell lymphomas. Jpn J Cancer Res 1997; 88: 1087–1093.

    Article  CAS  Google Scholar 

  22. Jewell SD, Srinivasan M, McCart LM, Williams N, Grizzle WH, LiVolsi V et al. Analysis of the molecular quality of human tissues: an experience from the Cooperative Human Tissue Network. Am J Clin Pathol 2002; 118: 733–741.

    Article  CAS  Google Scholar 

  23. Seto M, Yamamoto K, Iida S, Akao Y, Utsumi KR, Kubonishi I et al. Gene rearrangement and overexpression of PRAD1 in lymphoid malignancy with t(11;14)(q13;q32) translocation. Oncogene 1992; 7: 1401–1406.

    CAS  PubMed  Google Scholar 

  24. Emig M, Saussele S, Wittor H, Weisser A, Reiter A, Willer A et al. Accurate and rapid analysis of residual disease in patients with CML using specific fluorescent hybridization probes for real time quantitative RT-PCR. Leukemia 1999; 13: 1825–1832.

    Article  CAS  Google Scholar 

  25. Snider JV, Wechser MA, Lossos IS . Human disease characterization: real-time quantitative PCR analysis of gene expression. Drug Discov Today 2001; 6: 1062–1067.

    Article  CAS  Google Scholar 

  26. Starostik P, Patzner J, Greiner A, Schwarz S, Kalla J, Ott G et al. Gastric marginal zone B-cell lymphomas of MALT type develop along 2 distinct pathogenetic pathways. Blood 2002; 99: 3–9.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported in part by a Grant-in-Aid for the development of a model system for the organization of biotechnological industry information from the Japan Biological Informatics Consortium, and a Grant-in-Aid for the Second-Term Comprehensive 10-year Strategy for Cancer Control from the Ministry of Health and Welfare, a Grant-in-Aid for Science on Primary Areas (Cancer Research) and a Grant-in-Aid for the Encouragement of Young Scientists from the Ministry of Education, Science and Culture, Japan.

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Authors and Affiliations

  1. Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan

    M Suguro-Katayama, R Suzuki, Y Kasugai, H Suzuki, Y Hosokawa & M Seto

  2. Second Department of Internal Medicine, Mie University School of Medicine, Mie, Japan

    M Suguro-Katayama & H Shiku

  3. Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan

    T Nakamura

  4. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan

    S Nakamura

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  1. M Suguro-Katayama
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Suguro-Katayama, M., Suzuki, R., Kasugai, Y. et al. Heterogeneous copy numbers of API2-MALT1 chimeric transcripts in mucosa-associated lymphoid tissue lymphoma. Leukemia 17, 2508–2512 (2003). https://doi.org/10.1038/sj.leu.2403179

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