A novel fusion of the MALT1 gene and the microtubule-associated protein 4 (MAP4) gene occurs in diffuse large B-cell lymphoma

作者：Murga Penas Eva M; Kawadler Holli; Siebert Reiner; Frank Matthias; Ye Hongtao; Hinz Kristina; Becher Claudia; Hummel Michael; Barth Thomas F E; Bokemeyer Carsten; Stein Harald; Truemper Lorenz; Moeller Peter; Marynen Peter; Du Ming Qing; Yang Xiaolu; Hansmann Martin L; Dierlamm Judith^*

来源：Genes, Chromosomes and Cancer, 2006, 45(9): 863-873.

DOI：10.1002/gcc.20350

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-kappa B 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(I 1; 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-kappa B. As a result of the deletion, the reciprocal 5'MAP4-3'MALTI transcript was not present, demonstrating that the 5'MALTI-3'MAP4 fusion represents the pathogenetically relevant transcript. Immunohistochemistry with amino-terminal and carboxy-terminal MALT I antibodies, indicated a strong expression of the chimeric MALT1-MAP4 protein. Moreover, NF-kappa B activation was not increased in this case as shown by the levels of I kappa B alpha phosphorylation and NEMO ubiquitination. Our data demonstrate that the pathogenetic consequences of the novel MALTI-MAP4 fusion are different from those of the known MALT1-associated chromosomal rearrangements and do not involve NF-kappa B activation.

• 出版日期2006-9