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Mucosa-Associated Lymphoid Tissue Lymphoma: Novel Translocations Including Rearrangements of ODZ2, JMJD2C, and CNN3

Authors' Affiliations: Departments of ¹ Pathology and ² Internal Medicine 1, Medical University of Vienna, Vienna, Austria

Requests for reprints: Berthold Streubel, Department of Pathology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. Phone: 431-40400-3650; Fax: 431-40400-3707; E-mail: berthold.streubel{at}meduniwien.ac.at.

Purpose: The well-known translocations identified in MALT lymphomas include t(11;18)/API2-MALT1, t(1;14)/IGH-BCL10, and t(14;18)/IGH-MALT1. Molecular investigations have suggested that these three disparate translocations affect a common pathway, resulting in the constitutive activation of nuclear factor-B. However, the vast majority of MALT lymphomas are negative for any of the above-mentioned translocations and the underlying pathogenesis is unclear.

Experimental Design: Fresh tissue of 29 gastric and extragastric MALT lymphomas was studied for genetic aberrations by conventional karyotyping, long-distance inverse PCR (LDI-PCR), fluorescence in situ hybridization (FISH), reverse transcription-PCR (RT-PCR), and real-time quantitative RT-PCR (QRT-PCR).

Results: Conventional cytogenetics, FISH, and RT-PCR identified aberrations in 26 of 29 MALT lymphoma. Balanced translocations were found in 21 cases. IGH was rearranged in the majority of cases with balanced translocations (n = 17/21); 3 cases had t(11;18)/API2-MALT1 and 1 case had novel t(6;7)(q25;q11), respectively. IGH partner genes involved MALT1, FOXP1, BCL6, and four new chromosomal regions on chromosome arms 1p, 1q, 5q, and 9p. LDI-PCR identified three novel partner genes on 1p (CNN3), 5q (ODZ2), and 9p (JMJD2C). FISH assays were established and confirmed LDI-PCR results. QRT-PCR showed deregulation of the novel genes in the translocation-positive cases.

Conclusions: Our study expands the knowledge on the genetic heterogeneity of MALT lymphomas.