Genetic heterogeneity of DLBCL, not otherwise specified

Diffuse large B-cell lymphoma (DLBCL), not otherwise specified, is the most common malignant lymphoma in the world. The recent progress of molecular techniques has proved its heterogeneity. Gene expression profiling for DLBCL, recently achieved using formalin-fixed paraffin-embedded samples, has identified two molecular subtypes, according to their cell of origin correlated with prognosis. Genomic abnormalities are roughly divided into translocations, amplifications/deletions, and mutations. Translocations involving MYC and BCL2 frequently co-occur in 5%-10% of DLBCL and are associated with aggressive clinical behavior with poor outcomes. Array CGH has identified some genetic alterations including deletions of tumor suppressor genes, such as CDKN2A, and amplifications of several genes involved in oncogenic pathway, such as NFκB. The next generation sequence identified numerous somatic gene mutations in DLBCL. Mutations of epigenome-associated genes, tumor suppressor genes, and NFκB-associated genes have been identified in cases of DLBCL. These mutations affect the function of gene products and play important roles in lymphomagenesis or the progression of DLBCL. This fact suggested that these mutations may affect clinicopathological findings, particularly prognosis. In this study, the most recent advances in genetic alterations and their association with clinicopathological findings of DLBCL were introduced and reviewed.