Molecular Pathogenesis of Diffuse Large B-Cell Lymphoma

抄録

Diffuse large B-cell lymphoma (DLBCL) is divided into germinal center B-like (GCB) DLBCL and activated B-like (ABC) DLBCL. In recent years, whole genome sequencing (WGS), whole exome sequencing (WES), and transcriptome sequencing (RNA-seq) have been performed for samples from many patients with DLBCL. Here, I present a review of the results of next generation sequencing data for DLBCL. Somatic mutations show a low identity between studies with only 10–20% gene overlap. DLBCL is a disease that results from various molecular pathogeneses. Mutations in genes involved in chromatin remodeling were found in the GCB subtype. Mutations in members of B-cell receptor (BCR) signaling and the NF-κB pathway (MYD88) were found in the ABC subtype. The MYD88 L265P mutation was observed in 29% of ABC DLBCL cases. EZH2 mutations were observed in 21.7% of GCB DLBCL cases. WGS indicated that inactivating mutations in GNA13 (Gα protein) were prevalent in GCB DLBCL cases. In addition, S1PR2 is a target of aberrant somatic hypermutation. In recent years, samples from patients with relapsed and refractory DLBCL were analyzed. The activation of the NF-κB pathway is associated with treatment resistance in DLBCL. Further clarification of the molecular pathogenesis of DLBCL is expected to lead to the development of individualized treatment for the disease.