Identification of cell-type-specific mutations in nodal T-cell lymphomas.
Identification of cell-type-specific mutations in nodal T-cell lymphomas.
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DOI：
10.1038/bcj.2016.122
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发表时间：
2017-01-06
影响因子：
12.8
通讯作者：
Chiba S
中科院分区：
文献类型：
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作者：
Nguyen TB;Sakata-Yanagimoto M;Asabe Y;Matsubara D;Kano J;Yoshida K;Shiraishi Y;Chiba K;Tanaka H;Miyano S;Izutsu K;Nakamura N;Takeuchi K;Miyoshi H;Ohshima K;Minowa T;Ogawa S;Noguchi M;Chiba S
最近的遗传分析发现，在淋巴结t细胞淋巴瘤（包括血管免疫母细胞t细胞淋巴瘤和外周t细胞淋巴瘤）中，10 - 11易位2 （TET2）、DNA甲基转移酶3A （DNMT3A）、异柠檬酸脱氢酶2 （IDH2）和ras同源家族成员A （RHOA）中经常发生突变。我们研究了这些成熟T-/自然杀伤细胞肿瘤亚型的突变分布，以确定它们的克隆结构。对87例肿瘤源性DNA中的71个基因进行了靶向测序。然后在19例病例的程序性死亡-1 （PD1）阳性人群中分析突变，这些人群富含肿瘤细胞和cd20阳性B细胞，这些细胞通过激光显微解剖纯化。在15/16和4/7的PD1+细胞和CD20+细胞中分别检测到TET2和DNMT3A突变。所有RHOA和IDH2突变都局限于PD1+细胞，这表明包括RHOA和IDH2突变在内的一些突变是肿瘤细胞中的特异性事件。值得注意的是，我们发现所有NOTCH1突变仅在CD20+细胞中检测到。总之，我们确定了B细胞和T细胞特异性突变，以及T细胞和B细胞共同的突变。这些发现表明，在基因突变的多步骤和多系获得后，克隆的扩展。
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.