Exome sequencing identifies frequent mutation of MLL2 in non-small cell lung carcinoma from Chinese patients.
Exome sequencing identifies frequent mutation of MLL2 in non-small cell lung carcinoma from Chinese patients.
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外显子组测序发现中国非小细胞肺癌患者中 MLL2 频繁突变
DOI：
10.1038/srep06036
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发表时间：
2014-08-12
影响因子：
4.6
通讯作者：
Kong X
中科院分区：
文献类型：
--
作者：
Yin S;Yang J;Lin B;Deng W;Zhang Y;Yi X;Shi Y;Tao Y;Cai J;Wu CI;Zhao G;Hurst LD;Zhang J;Hu L;Kong X
肺癌是全世界癌症死亡的最常见原因，估计每年有140万人死亡。在这里，我们报告了9个肿瘤/正常组织对中国非小细胞肺癌（NSCLC）患者的全外显子组测序。这使得我们能够鉴定出NSCLC中大量显著突变的基因，这些基因在DNA损伤修复、NF-κB通路、JAK/STAT信号传导和染色质修饰中高度富集。值得注意的是，我们发现组蛋白-赖氨酸甲基转移酶基因，即MLL 2，是我们筛选中突变最显着的基因之一。在随后的验证研究中，我们在105例NSCLC患者中的12例（11.4%）中鉴定了MLL 2的有害突变。此外，与配对的相邻非肿瘤组织相比，无论突变状态如何，通常在肿瘤组织中观察到MLL 2表达减少或缺失。总之，我们的研究定义了中国NSCLC的体细胞突变的景观，并支持MLL 2突变在疾病发病机制中的作用。
Lung cancer is the most common cause of cancer mortality worldwide, with an estimated 1.4 million deaths each year. Here we report whole-exome sequencing of nine tumor/normal tissue pairs from Chinese patients with non-small cell lung carcinoma (NSCLC). This allows us to identify a number of significantly mutated genes in NSCLC, which were highly enriched in DNA damage repair, NF-κB pathway, JAK/STAT signaling and chromatin modification. Notably, we identify a histone-lysine methyltransferase gene, namely, MLL2, as one of the most significantly mutated genes in our screen. In a following validation study, we identify deleterious mutations of MLL2 in 12 out of 105 (11.4%) NSCLC patients. Additionally, reduced or lost expression of MLL2 was commonly observed in tumor tissues as compared with paired adjacent non-tumor tissues regardless of mutation status. Together, our study defines the landscape of somatic mutations in Chinese NSCLC and supports the role of MLL2 mutation in the pathogenesis of the disease.