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

Abstract

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-nB. 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 21cases. IGH was rearranged in the majority of cases with balanced translocations (n = 17/21); 3 cases had t(11;18)/API2-MALT1 and 1case 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.

From MALT lymphoma to the CBM signalosome

“…These include t(1;14)(p21;q32), t(5;14)(q34;q32), t(9;14)(p24;q32) and t(3;14)(p13;q32), which result in placement of the CNN3, ODZ2, JMJD2C and FOXP1 genes, respectively, downstream of the IGH promoter element. [29][30][31] Detailed information regarding the many genetic abnormalities associated with MALT lymphoma has been provided in a recent review in reference 32.…”

Chronic inflammatory disease, lymphoid tissue neogenesis and extranodal marginal zone B-cell lymphomas

“…[128][129][130][131]142,143 More recently, three novel IgH translocations in non-gastric MZBCL involving ODZ2, CNN3 and JMJD2C have been described, of which ODZ2 and JMJD2C were found recurrently. 144 The t(11;18) is present in ~40% of pulmonary-and iñ 20% of gastric-MZBCLs and is virtually absent in MZBCLs of the salivary gland (Table 2). 86,[128][129][130][131][132][133][134] Gastric MZBCLs harboring the t(11;18) were found to be associated with CagA-positive strains of H. pylori.…”

T(14;18)(q32;q21) involving MALT1 and IGH genes occurs in extranodal diffuse large B-cell lymphomas of the breast and testis

“…26,46,47 We did not detect any new or recently described sporadic translocations, such as t(6;7)(q25;q11), 48 t(X;14)(p11.4;q32), 49 and translocations involving chromosomal regions on chromosome arms 1p, 1q, 5q and 9p. 48 No loss or amplification of any of the studied regions was seen.…”

“…26,46,47 We did not detect any new or recently described sporadic translocations, such as t(6;7)(q25;q11), 48 t(X;14)(p11.4;q32), 49 and translocations involving chromosomal regions on chromosome arms 1p, 1q, 5q and 9p. 48 No loss or amplification of any of the studied regions was seen.Similarly to other studies we found that trisomies 3 and 18 were the most common numerical aberrations in extranodal marginal zone lymphoma, 14,17,24,27,31,32,35,50,51 and extranodal diffuse Table 1 Clinicopathological and FISH data of extranodal marginal zone lymphoma and diffuse large B-cell lymphoma of the thyroid, testis and breast for detection of t(11;18)(q21;q21) (t(1;14)(p22;q32), t(14;18)(q32;q21) involving IGH/MALT1 and IGH/BCL-2 and numerical aberrations of chromosomes 1, 3, 12 and 18 …”