Activating somatic mutations in diffuse large B-cell lymphomas: lessons from next generation sequencing and key elements in the precision medicine era

作者：Bohers Elodie; Mareschal Sylvain; Bertrand Philippe; Viailly Pierre Julien; Dubois Sydney; Maingonnat Catherine; Ruminy Philippe; Tilly Herve; Jardin Fabrice^*

来源：Leukemia and Lymphoma, 2015, 56(5): 1213-1222.

DOI：10.3109/10428194.2014.941836

• NGS
• diffuse large B-cell lymphoma
• somatic mutations
• targeted therapy

Diffuse large B-cell lymphoma (DLBCL) is the most common form of lymphoma, accounting for 30-40% of newly diagnosed non-Hodgkin lymphomas. Historically, DLBCL has been thought to involve recurrent translocations of the immunoglobulin heavy (IGH) locus and the deregulation of rearranged oncogenes. Whole exome sequencing (WES) of more than 200 DLBCLs has completely redefined the genetic landscape of the disease by identifying recurrent single nucleotide variants and providing new therapeutic opportunities in DLBCL molecular subtypes. Some of these somatic mutations target genes that play a crucial role in B-cell B cell receptor [BCR] signaling, nuclear factor kappa B [NF-kappa B] pathway, Toll-like receptor [TLR] signaling and phosphatidylinositol 3-kinase [PI3K] pathway), immunity, cell cycle/apoptosis or chromatin modification. In this review, following an overview of the somatic mutations reported in DLBCL, we focus on activating and clustered mutations targeting genes including MYD88, CD79A/B, EZH2 and CARD11 and discuss their clinical and therapeutic relevance in the precision medicine era.

• 出版日期2015-5