Zheng Mei, Perry Anamarija M, Bierman Philip, Loberiza Fausto, Nasr Michel R, Szwajcer David, Del Bigio Marc R, Smith Lynette M, Zhang Weiwei, Greiner Timothy C
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada.
Neuropathology. 2017 Dec;37(6):509-516. doi: 10.1111/neup.12405. Epub 2017 Aug 30.
Primary CNS diffuse large B-cell lymphoma (PCNS-DLBCL) and systemic DLBCL harbor mutations in MYD88 and CD79B. DNA methyltransferase (MGMT) is methylated in some DLBCL. Our goal was to investigate the frequencies of these events, which have not been previously reported within the same series of patients with PCNS-DLBCL. Fifty-four cases of PCNS-DLBCL from two institutions were analyzed by Sanger sequencing for MYD88 and CD79B, and pyrosequencing for MGMT. MYD88 mutations were identified in 68.8% (35 of 51 cases), with L265P being the most frequent mutation. Mutations other than L265P were identified in 21.6% of cases, of which eight novel MYD88 mutations were identified. Of mutated cases, 17.6% had homozygous/hemizygous MYD88 mutations, which has not been previously reported in PCNS-DLBCL. CD79B mutations were found in six of 19 cases (31.6%), all in the Y196 mutation hotspot. MGMT methylation was observed in 37% (20 of 54 cases). There was no significant difference in median overall survival (OS) between the wild type and mutated MYD88 cases, or between methylated and unmethylated MGMT cases. However, a significant difference (P = 0.028) was noted in median OS between the wild type and mutated CD79B cases.
原发性中枢神经系统弥漫性大B细胞淋巴瘤（PCNS-DLBCL）和系统性弥漫性大B细胞淋巴瘤（systemic DLBCL）存在MYD88和CD79B基因突变。部分弥漫性大B细胞淋巴瘤中DNA甲基转移酶（MGMT）发生甲基化。我们的目标是调查这些事件的发生频率，此前在同一组PCNS-DLBCL患者中尚未有相关报道。对来自两家机构的54例PCNS-DLBCL病例进行Sanger测序分析MYD88和CD79B，焦磷酸测序分析MGMT。在68.8%（51例中的35例）的病例中检测到MYD88突变，其中L265P是最常见的突变。在21.6%的病例中检测到非L265P突变，其中鉴定出8种新的MYD88突变。在发生突变的病例中，17.6%有纯合/半合子MYD88突变，这在PCNS-DLBCL中此前未见报道。在19例中的6例（31.6%）发现CD79B突变，均位于Y196突变热点区域。在37%（54例中的20例）观察到MGMT甲基化。野生型和MYD88突变型病例之间，以及甲基化和未甲基化MGMT病例之间的中位总生存期（OS）无显著差异。然而，野生型和CD79B突变型病例之间的中位OS存在显著差异（P = 0.028）。
