Inactivating mutations and overexpression of BCL 10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32)

Quangeng Zhang, Reiner Siebert, Minhong Yan, Bernd Hinzmann, Xiaoli Cui, Liquan Xue, Karen M. Rakestraw, Clayton W. Naeve, Georg Beckmann, Dennis D. Weisenburger, Warren G. Sanger, Hadwiga Nowotny, Michael Vesely, Evelyne Callet-Bauchu, Gilles Salles, Vishva M. Dixit, André Rosenthal, Brigitte Schlegelberger, Stephan W. Morris

Research output: Contribution to journalArticlepeer-review

329 Scopus citations

Abstract

Mucosa-associated lymphoid tissue (MALT) lymphomas most frequently involve the gastrointestinal tract and are the most common subset of extranodal non-Hodgkin lymphoma (NHL). Here we describe overexpression of BCL10, a novel apoptotic signalling gene that encodes an amino-terminal caspase recruitment domain (CARD; ref. 2), in MALT lymphomas due to the recurrent t(1;14)(p22;q32)(ref. 3). BCL10 CDNAs from t(1;14)-positive MALT tumours contained a variety of mutations, most resulting in truncations either in or carboxy terminal to the CARD. Wild-type BCL10 activated NF-κB but induced apoptosis of MCF7 and 293 cells. CARD-truncation mutants were unable to induce cell death or activate NF-κB, whereas mutants with C- terminal truncations retained NF-κB activation but did not induce apoptosis. Mutant BCL10 overexpression might have a twofold lymphomagenic effect: loss of BCL10 pro-apoptosis may confer a survival advantage to MALT B-cells, and constitutive NF-κB activation may provide both anti-apoptotic and proliferative signals mediated via its transcriptional targets.

Original languageEnglish (US)
Pages (from-to)63-68
Number of pages6
JournalNature Genetics
Volume22
Issue number1
DOIs
StatePublished - May 1999

ASJC Scopus subject areas

  • Genetics

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