title: Activating somatic mutations in diffuse large B-cell lymphomas: lessons from next generation sequencing and key elements in the precision medicine era.
abstract: 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 function (B cell receptor [BCR] signaling, nuclear factor κB [NF-κB] 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.
authors.affiliation: INSERM U918, Centre Henri Becquerel, Rouen University and IRIB , Rouen , France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Bohers
authors.forename: Sylvain
authors.initials: S
authors.lastname: Mareschal
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertrand
authors.forename: Pierre Julien
authors.initials: PJ
authors.lastname: Viailly
authors.forename: Sydney
authors.initials: S
authors.lastname: Dubois
authors.forename: Catherine
authors.initials: C
authors.lastname: Maingonnat
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruminy
authors.forename: Hervé
authors.initials: H
authors.lastname: Tilly
authors.forename: Fabrice
authors.initials: F
authors.lastname: Jardin
mesh_terms: D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D058990:Molecular Targeted Therapy; D009154:Mutation; D057285:Precision Medicine; D015398:Signal Transduction
keywords: NGS; diffuse large B-cell lymphoma; somatic mutations; targeted therapy