Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, 135-710.
Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea, 135-710.
Hum Pathol. 2014 Mar;45(3):556-64. doi: 10.1016/j.humpath.2013.10.023. Epub 2013 Oct 31.
Mutations in 2 upstream components of the nuclear factor κB (NF-κB) pathway, CD79B and MYD88, are important information for new target therapy in malignant lymphoma. We examined the prevalence and clinicopathologic characteristics of CD79B and MYD88 mutation in a cohort of Asian diffuse large B cell lymphoma (DLBCL) patients. CD79B and MYD88 mutations were analyzed by Sanger sequencing in 187 DLBCL tissue samples. CD79B immunoreceptor tyrosine-based activation motif spanning exon 5 and 6 and MYD88 TIR domain spanning exons 3, 4 and 5 were amplified and sequenced. The cell-of-origin was determined based on immunohistochemical stains for CD10, BCL-6 and MUM-1 by Hans' algorithm. CD79B was mutated in 16 cases (8.5%), mostly involving the first tyrosine (Y196) of immunoreceptor tyrosine-based activation motif. For MYD88, L265P mutation was found in 31 cases (out of 161, 19.3%). In 11 of these, a CD79B mutation coexisted, which constituted 69% of CD79B mutants and 36% of MYD88 L265P cases. Clinicopathologic comparison between the mutant and the wild-type group showed that the mean age was older for both CD79B (66 versus 58 years) and MYD88 L265P mutant groups (64 versus 58 years). Survival analyses showed that neither CD79B mutation nor MYD88 L265P was a significant prognostic indicator. In conclusion, CD79B and MYD88 mutations are associated with an older age at onset in DLBCL with a significant overlap, which did not affect the outcome of the disease.
CD79B 和 MYD88 是核因子 κB（NF-κB）通路的两个上游组件的突变，是恶性淋巴瘤新靶向治疗的重要信息。我们在一组亚洲弥漫性大 B 细胞淋巴瘤（DLBCL）患者中检查了 CD79B 和 MYD88 突变的流行率和临床病理特征。通过 Sanger 测序分析了 187 例 DLBCL 组织样本中的 CD79B 和 MYD88 突变。扩增并测序了 CD79B 免疫受体酪氨酸激活基序跨越外显子 5 和 6 和 MYD88 TIR 域跨越外显子 3、4 和 5。根据 Hans 算法的 CD10、BCL-6 和 MUM-1 的免疫组化染色确定了细胞起源。CD79B 突变发生在 16 例（8.5％）中，主要涉及免疫受体酪氨酸激活基序的第一个酪氨酸（Y196）。对于 MYD88，发现 L265P 突变发生在 31 例（161 例中的 31 例，占 19.3％）中。在其中的 11 例中，存在 CD79B 突变，占 CD79B 突变体的 69％和 MYD88 L265P 病例的 36％。突变体与野生型组之间的临床病理比较表明，CD79B（66 岁与 58 岁）和 MYD88 L265P 突变组（64 岁与 58 岁）的平均年龄较大。生存分析表明，CD79B 突变或 MYD88 L265P 均不是疾病预后的显著指标。总之，CD79B 和 MYD88 突变与 DLBCL 的发病年龄较大相关，且具有显著重叠性，但不会影响疾病的结局。
