Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hematol Oncol. 2022 Dec;40(5):885-893. doi: 10.1002/hon.3073. Epub 2022 Sep 10.
Diffuse large B-cell lymphoma (DLBCL) is a group of heterogeneous tumors with different molecular traits and clinical features. MYD88 is an oncogene that activates the nuclear factor κB pathway in DLBCL. MYD88 L265P mutation frequently occurs in DLBCL with poor prognosis, while the clinical significance of non-L265P mutations needs to be clarified. Next-generation sequencing was performed on a cohort of 356 patients with DLBCL to investigate the impact of MYD88 mutation. Ten MYD88 mutated variants were detected in 32% (114/356) of the cases. V217F, S219C, S222R, M232T, S243N, and T294P were identified as pathogenic variants. MYD88 non-L265P mutations occurred less than L265P mutation in DLBCL of the central nervous system and breast tissue. The coexistence of MYD88 non-L265P mutations with PIM1 mutation was also less than that of L265P mutation. The progression-free survival in patients with DLBCL with MYD88 non-L265P mutation was statistically better than in patients with MYD88 L265P mutation. The interpretation of variants of MYD88 mutation offers a precise guide for the management of DLBCL.
弥漫性大 B 细胞淋巴瘤（DLBCL）是一组具有不同分子特征和临床特征的异质性肿瘤。MYD88 是一种癌基因，可激活 DLBCL 中的核因子 κB 途径。MYD88 L265P 突变在预后不良的 DLBCL 中频繁发生，而非 L265P 突变的临床意义尚需阐明。对 356 例 DLBCL 患者进行了下一代测序，以研究 MYD88 突变的影响。在 32%（356 例中的 114 例）的病例中检测到 10 种 MYD88 突变变体。鉴定出 V217F、S219C、S222R、M232T、S243N 和 T294P 为致病性变体。MYD88 非 L265P 突变在中枢神经系统和乳腺组织的 DLBCL 中比 L265P 突变少见。MYD88 非 L265P 突变与 PIM1 突变共存的情况也少于 L265P 突变。具有 MYD88 非 L265P 突变的 DLBCL 患者的无进展生存期在统计学上优于具有 MYD88 L265P 突变的患者。对 MYD88 突变变体的解释为 DLBCL 的管理提供了精确的指导。
