Targetable activating mutations are very frequent in GCB and ABC diffuse large B‐cell lymphoma. Issue 2 (5th November 2013)

• Record Type: Journal Article
• Authors: Bohers, Elodie; Mareschal, Sylvain; Bouzelfen, Abdelilah; Marchand, Vinciane; Ruminy, Philippe; Maingonnat, Catherine; Ménard, Anne‐Lise; Etancelin, Pascaline; Bertrand, Philippe; Dubois, Sydney; Alcantara, Marion; Bastard, Christian; Tilly, Hervé; Jardin, Fabrice
• Is Part Of: Genes, chromosomes & cancer. Volume 53:Issue 2(2014:Feb.)
• Page Start: 144
• Page End: 153
• Publication Date: 2013-11-05
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22126
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Diffuse large B cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy that can be divided in two major subgroups, germinal center B‐cell‐like (GCB) and activated B‐cell‐like (ABC). Activating mutations of genes involved in the BCR and NF‐κB pathways (<italic>CD79A</italic>, <italic>CD79B</italic>, <italic>MYD88</italic>, and <italic>CARD11</italic>) or in epigenetic regulation (<italic>EZH2</italic>) have been recently reported, preferentially in one of the two DLBCL subtypes. We analyzed the mutational status of these five recurrently mutated genes in a cohort of 161 untreated de novo DLBCL. Overall, 93 mutations were detected, in 61 (38%) of the patients. The L265P <italic>MYD88</italic> mutation was the most frequent <italic>MYD88</italic> variant (<italic>n</italic> = 18), observed exclusively in the ABC subtype. CD79A/CD79B ITAM domains were targeted in ABC DLBCL (12/77; 16%), whereas <italic>CARD11</italic> mutations were equally distributed in the two subtypes. The <italic>EZH2</italic> Y641 substitution was found almost exclusively in the GCB subgroup (15/62; 24%). Twenty cases (12%) displayed two activating mutations, including the most frequent <italic>CD79/MYD88</italic> variants combination (<italic>n</italic> = 8) which is observed exclusively in the ABC subtype. When considering only ABC DLBCL patients treated by rituximab plus chemotherapy, the presence of an activating NF‐κB mutation was associated with an unfavorable outcome (3‐years OS 26% for mutated cases versus 67% for the cases without mutations, <italic>P</italic> = 0.0337). Our study demonstrates that activating and targetable mutations are observed at a very high frequency in DLBCL at the time of diagnosis, indicating that sequencing of a limited number of genes could help tailor an optimal treatment strategy in DLBCL. © 2013 Wiley Periodicals, Inc.</p> </abstract>