title: Molecular Pathogenesis of Diffuse Large B-Cell Lymphoma.
abstract: 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.
authors.affiliation: Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research.
authors.forename: Akito
authors.initials: A
authors.lastname: Dobashi
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics / Q000378:metabolism; D059472:Exome; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D049349:Receptors, Lysosphingolipid; D015398:Signal Transduction; D000081025:Sphingosine-1-Phosphate Receptors
chemical_list: C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D009363:Neoplasm Proteins; D011947:Receptors, Antigen, B-Cell; D049349:Receptors, Lysosphingolipid; C477522:S1PR2 protein, human; D000081025:Sphingosine-1-Phosphate Receptors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D043802:GTP-Binding Protein alpha Subunits, Gq-G11