Primary diffuse large B-cell lymphomas of central nervous system exhibit remarkably high prevalence of oncogenic MYD88 and CD79B mutations
Primary diffuse large B-cell lymphomas of central nervous system exhibit remarkably high prevalence of oncogenic MYD88 and CD79B mutations
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DOI：
10.3109/10428194.2014.979413
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发表时间：
2015-07-01
影响因子：
2.6
通讯作者：
Yamazaki, Kazuto
中科院分区：
文献类型：
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作者：
Yamada, So;Ishida, Yasuo;Yamazaki, Kazuto
MyD88和CD79B突变激活核因子-kappaB信号，在弥漫性大B细胞淋巴瘤(DLBCL)亚群中普遍存在。我们检测了18例原发性中枢神经系统(CNS)DLBCL中MYD88的Toll/IL-1受体(TIR)结构域和CD79A/B的酪氨酸激活基序(ITAM)结构域的体细胞突变发生率及其免疫学特征。17例(94.4%)出现MyD88突变，均为L265P突变。CD79B突变11例(61.1%)，其中Vi 96C/D/H突变10例(55.6%)。CD79A基因突变完全缺失。免疫组织化学均为CD3-/CD5-/CD20+/CD79a+/GCET1-/BCL6+/MUM1+。CD10+3例(16.7%)，CD10-15例(83.3%)。总体而言，所有病例都携带MYD88(L265P)或CD79B(Y196C/D/H)，或两者兼有，无论其免疫学特征如何。我们的结果表明，CNS DLBCL是一组具有特征性突变特征的肿瘤，它在免疫特权部位触发核因子-kappaB信号。
MYD88 and CD79B mutations that activate nuclear factor (NF)-kappa B 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 Vi 96C/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-kappa B signaling in the immune-privileged site.