title: Primary diffuse large B-cell lymphomas of central nervous system exhibit remarkably high prevalence of oncogenic MYD88 and CD79B mutations.
abstract: MYD88 and CD79B mutations that activate nuclear factor (NF)-κB signaling are prevalent in subsets of diffuse large B-cell lymphoma (DLBCL). We examined the prevalence of somatic mutations in the Toll/interleukin-1 receptor (TIR) domain of MYD88 and the tyrosine-based activation motif (ITAM) domain of CD79A/B in 18 primary central nervous system (CNS) DLBCLs, and their immunoprofile. MYD88 mutation was found in 17 cases (94.4%), all of which were L265P substitutions. CD79B mutation was found in 11 cases (61.1%), 10 (55.6%) of which were Y196C/D/H substitutions. Mutation of CD79A was completely absent. Immunohistochemically, all the tumors were CD3-/CD5-/CD20+/CD79a+/ GCET1-/BCL6+/MUM1+. Three (16.7%) cases were CD10+, but the majority (15 cases, 83.3%) were CD10-. Overall, all cases harbored either MYD88(L265P) or CD79B(Y196C/D/H), or both, irrespective of their immunoprofile. Our results suggest that CNS DLBCL is a group of tumors harboring a characteristic mutation profile which triggers NF-κB signaling in the immune-privileged site.
authors.affiliation: Department of Neurosurgery, Teikyo University, Chiba Medical Center , Ichihara , Japan.
authors.forename: So
authors.initials: S
authors.lastname: Yamada
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ishida
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuno
authors.forename: Kazuto
authors.initials: K
authors.lastname: Yamazaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051925:CD79 Antigens / Q000235:genetics*; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D009367:Neoplasm Staging; D015995:Prevalence; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies
chemical_list: D051925:CD79 Antigens; C497883:CD79B protein, human; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88
keywords: CD79B; Central nervous system; MYD88; lymphoma; mutation