文章：

识别淋巴结T细胞淋巴瘤中特定细胞类型的突变

Identification of cell-type-specific mutations in nodal T-cell lymphomas

原文发布日期：2017-01-06

DOI: 10.1038/bcj.2016.122

类型: Original Article

开放获取: 是

英文摘要：

Recent genetic analysis has identified frequent mutations in ten-eleven translocation 2 (TET2), DNA methyltransferase 3A (DNMT3A), isocitrate dehydrogenase 2 (IDH2) and ras homolog family member A (RHOA) in nodal T-cell lymphomas, including angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified. We examined the distribution of mutations in these subtypes of mature T-/natural killer cell neoplasms to determine their clonal architecture. Targeted sequencing was performed for 71 genes in tumor-derived DNA of 87 cases. The mutations were then analyzed in a programmed death-1 (PD1)-positive population enriched with tumor cells and CD20-positive B cells purified by laser microdissection from 19 cases. TET2 and DNMT3A mutations were identified in both the PD1+ cells and the CD20+ cells in 15/16 and 4/7 cases, respectively. All the RHOA and IDH2 mutations were confined to the PD1+ cells, indicating that some, including RHOA and IDH2 mutations, being specific events in tumor cells. Notably, we found that all NOTCH1 mutations were detected only in the CD20+ cells. In conclusion, we identified both B- as well as T-cell-specific mutations, and mutations common to both T and B cells. These findings indicate the expansion of a clone after multistep and multilineal acquisition of gene mutations.

摘要翻译： 

近期遗传学分析发现，在淋巴结T细胞淋巴瘤（包括血管免疫母细胞性T细胞淋巴瘤及非特指型外周T细胞淋巴瘤）中，TET2、DNMT3A、IDH2与RHOA基因频繁发生突变。为解析其克隆架构，我们考察了这些成熟T细胞/NK细胞肿瘤亚型的突变分布情况。研究人员对87例肿瘤来源DNA中的71个基因进行靶向测序，随后从19例样本中通过激光显微切割分离出富含肿瘤细胞的PD1阳性群体及CD20阳性B细胞，并对这些群体的突变进行分析。结果显示，在15/16的病例中检测到PD1+细胞与CD20+细胞同时存在TET2突变，4/7的病例中同时存在DNMT3A突变。而所有RHOA与IDH2突变均仅见于PD1+细胞，表明包括RHOA与IDH2在内的某些突变为肿瘤细胞特异性事件。值得注意的是，所有NOTCH1突变仅存在于CD20+细胞中。本研究最终鉴定出B细胞特异性突变、T细胞特异性突变以及T、B细胞共有突变，这些发现揭示了基因突变经多步骤、多谱系积累后引发的克隆扩增现象。

原文链接：

Identification of cell-type-specific mutations in nodal T-cell lymphomas