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

Penas, Eva Maria Murga; Hinz, Kristina; Röser, Kerstin; Copie‐Bergman, Christiane; Włodarska, Iwona; Marynen, Peter; Hagemeijer, Anne; Gaulard, Philippe; Löning, Thomas; Hossfeld, D. K.; Dierlamm, Judith

doi:10.1038/sj.leu.2403122

Cited by 87 publications

(67 citation statements)

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“…FISH data were collected using an Olympus BX 61 fluorescence microscope equipped with a cooled black-and-white camera controlled by the associated software (Olympus, Italy). 23,24 Statistical Analysis…”

Section: Fluorescent In Situ Hybridization Studymentioning

confidence: 99%

Nuclear bcl10 expression characterizes a group of ocular adnexa MALT lymphomas with shorter failure-free survival

Franco

Camacho

Caleo³

et al. 2006

Modern Pathology

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Ocular adnexa B-cell lymphomas are a relatively rare group of extranodal lymphomas, marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphomas) being the most frequent type at this location. As with other nongastrointestinal MALT lymphomas, ocular adnexa MALT lymphomas have distinct characteristics from those of the gastric MALT model, implying specific pathogenic events, which could be of interest in the prediction of clinical behavior and the choice between therapeutic options. In a series of 39 cases of ocular adnexa MALT lymphomas, studied using a tissue microarray, we observed that the most frequent alteration was related to apoptosis regulation. Thus, caspase 3 activity was completely abolished, and phosphorylated IjBa, a marker of NF-jB activation, showed increased expression, while cases with an increased number of large cells displayed increased expression of survivin and other cell-cycle-related proteins, such as cyclin A, cyclin E and Ki67, and p16 expression was reduced. There were no occurrences of t(11;18)(q21,q21), while 5/37 cases exhibited t(14;18)(q32;q21). Aberrant nuclear expression of bcl10 was observed in 11 cases, independently of the presence of translocations, and was significantly associated with phosphorylated IjBa expression and a reduced TdT-mediated biotin-dUTP nicked-end labeling apoptotic index. Moreover, patients with tumoral bcl10 nuclear expression showed shorter failure-free survival.

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Section: Fluorescent In Situ Hybridization Studymentioning

confidence: 99%

Nuclear bcl10 expression characterizes a group of ocular adnexa MALT lymphomas with shorter failure-free survival

Franco

Camacho

Caleo³

et al. 2006

Modern Pathology

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“…Several studies have looked for extranodal marginal zone lymphoma-associated translocations in breast lymphomas. [13][14][15]27,[38][39][40] T(18q21), involving MALT1, has not been found in any of the 36 extranodal marginal zone lymphomas and 14 diffuse large B-cell lymphomas [13][14][15]27,[38][39][40] of the breast that have been reported to date. There are no reports of extranodal marginal zone lymphoma-associated translocations in testicular diffuse large B-cell lymphoma, as the presence of extranodal marginal zone lymphoma components in testicular diffuse large B-cell lymphoma has been described only recently.…”

Section: Discussionmentioning

confidence: 99%

“…12 Four mutually exclusive and apparently sitespecific, chromosomal translocations have been implicated in the development and progression of extranodal marginal zone lymphoma of mucosaassociated lymphoid tissue. These extranodal marginal zone lymphoma-associated translocations, t(11;18)(q21;q21), 11,13-22 t(1;14)(p22;q32), 13,14,23 t(14;18) (q32;q21) 14,15,24,25 and t(3;14) 8,15,17,[27][28][29][30][31][32][33][34][35] One may wonder whether these extranodal marginal zone lymphoma-associated translocations and numerical aberrations occur in extranodal diffuse large B-cell lymphoma with marginal zone lymphoma components, which may belong to the extranodal marginal zone lymphoma spectrum.This study investigated for the presence of extranodal marginal zone lymphoma-associated translocations and numerical aberrations in diffuse large B-cell lymphoma with and without extranodal marginal zone lymphoma components and in extranodal marginal zone lymphoma of the breast, testis and thyroid, to test the hypothesis that also these lymphomas may belong to the spectrum of extranodal marginal zone lymphoma. …”

mentioning

confidence: 99%

mentioning

confidence: 99%

“…In addition, several studies have reported the presence of various cytogenetic numerical aberrations, including trisomy 3, 7, 12 and 18, in extranodal marginal zone lymphoma at different extranodal sites. 8,15,17,[27][28][29][30][31][32][33][34][35] One may wonder whether these extranodal marginal zone lymphoma-associated translocations and numerical aberrations occur in extranodal diffuse large B-cell lymphoma with marginal zone lymphoma components, which may belong to the extranodal marginal zone lymphoma spectrum.…”

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confidence: 99%

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

et al. 2013

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Primary B-cell lymphoma of the testis, breast and thyroid are rare and data concerning cytogenetic aberrations at these extranodal sites are scarce. We examined the presence of extranodal marginal zone lymphomaassociated translocations, t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), t(3;14)(p14.1;q32) and numerical aberrations of chromosomes 1, 3, 12 and 18 by fluorescence in situ hybridization in 6 extranodal marginal zone lymphomas and 24 diffuse large B-cell lymphomas with (n ¼ 9) or without (n ¼ 15) marginal zone lymphoma components, with primary localizations in the breast (n ¼ 15), testis (n ¼ 9) and thyroid (n ¼ 6). We found t(14;18)(q32;q21), with breakpoints in IGH and MALT1, in one testicular diffuse large B-cell lymphoma and in two diffuse large B-cell lymphomas of the breast. No other translocations, amplifications or deletions involving IGH, BCL-10, BCL-2, MALT1 and IAP2 were detected. Numerical aberrations occurred in 67% of the lymphomas, 67% of extranodal marginal zone lymphomas, 56% of diffuse large B-cell lymphomas with marginal zone lymphoma components and in 73% of 'de novo' diffuse large B-cell lymphomas. These included 78% of testis, 67% of thyroid and 60% of breast lymphomas, and included mainly trisomy 18 (n ¼ 16), trisomy 3 (n ¼ 8) and trisomy 1 (n ¼ 3). One testicular diffuse large B-cell lymphoma harbored both t(14;18)(q32;q21) and trisomy 3. Our results indicate that at least a few cases of diffuse large B-cell lymphoma of the testis and the breast belong to the spectrum of extranodal marginal zone lymphoma. Modern Pathology (2013) 26, 421-427; doi:10.1038/modpathol.2012; published online 28 September 2012Keywords: B-cell lymphoma; FISH; IGH; MALT1; numerical chromosomal aberrations; translocations Primary B-cell lymphoma of the testis, breast and thyroid are rare, each accounting for between 0.5 and 2.5% of all non-Hodgkin's lymphomas (NHLs). [1][2][3][4][5][6] Diffuse large B-cell lymphoma is the most common histological entity at these extranodal sites. Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, commonly found in extranodal sites devoid of native lymphoid tissue, like the stomach, lung, salivary gland, thyroid and ocular adnexa, occur infrequently in the breast and testis. Although extranodal marginal zone lymphoma and diffuse large B-cell lymphoma are considered distinct clinicopathological entities in the World Health Organization (WHO) classification, 7 many extranodal diffuse large B-cell lymphomas have derived from a background of extranodal marginal zone lymphoma. [8][9][10][11] We found that a large subgroup of primary testicular diffuse large B-cell lymphoma has marginal zone lymphoma components, including small cell components and lymphoepithelial lesions. 12 Four mutually exclusive and apparently sitespecific, chromosomal translocations have been implicated in the development and progression of extranodal marginal zone lymphoma of mucosaassociated lymphoid tissue. These extranodal marginal zone lymphoma-associated translocations, t(11...

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A novel fusion of theMALT1 gene and the microtubule-associated protein 4 (MAP4) gene occurs in diffuse large B-cell lymphoma

Penas

Kawadler

Siebert

et al. 2006

Genes Chromosom. Cancer

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Rearrangements of the MALT1 gene by the t(11;18)(q21;q21) and t(14;18)(q32;q21) are the most frequent structural chromosomal abnormalities in MALT lymphomas. These translocations lead to fusions of BIRC3-MALT1 and IGH-MALT1 respectively, and activate the NF-kappaB pathway. Among 122 diffuse large B-cell lymphomas and 28 Burkitt's lymphomas screened by interphase FISH, we found two cases with a break within MALT1, but without a t(11;18) or a t(14;18). Molecular genetic analyses in one of these cases revealed a novel "in frame" fusion of exon 9 of MALT1 and exon 9 of the microtubule-associated protein 4 (MAP4) gene. The translocation was accompanied by a deletion of MALT1 sequences distal to the breakpoint including the caspase-like domain, which is essential for activation of NF-kappaB. As a result of the deletion, the reciprocal 5'MAP4-3'MALT1 transcript was not present, demonstrating that the 5'MALT1-3'MAP4 fusion represents the pathogenetically relevant transcript. Immunohistochemistry with amino-terminal and carboxy-terminal MALT1 antibodies, indicated a strong expression of the chimeric MALT1-MAP4 protein. Moreover, NF-kappaB activation was not increased in this case as shown by the levels of IkappaBalpha phosphorylation and NEMO ubiquitination. Our data demonstrate that the pathogenetic consequences of the novel MALT1-MAP4 fusion are different from those of the known MALT1-associated chromosomal rearrangements and do not involve NF-kappaB activation.

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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

Cited by 87 publications

References 25 publications

Nuclear bcl10 expression characterizes a group of ocular adnexa MALT lymphomas with shorter failure-free survival

Nuclear bcl10 expression characterizes a group of ocular adnexa MALT lymphomas with shorter failure-free survival

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

A novel fusion of theMALT1 gene and the microtubule-associated protein 4 (MAP4) gene occurs in diffuse large B-cell lymphoma

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