外显子组测序鉴定出 MXRA5 是中国非小细胞肺癌患者中经常发生突变的新型癌症基因。
Exome sequencing identifies MXRA5 as a novel cancer gene frequently mutated in non-small cell lung carcinoma from Chinese patients.
机构信息
Department of Pharmacology and Toxicology and Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
出版信息
Carcinogenesis. 2012 Sep;33(9):1797-805. doi: 10.1093/carcin/bgs210. Epub 2012 Jun 13.
Abstract
Lung cancer has become the top killer among malignant tumors in China and is significantly associated with somatic genetic alterations. We performed exome sequencing of 14 non-small cell lung carcinomas (NSCLCs) with matched adjacent normal lung tissues extracted from Chinese patients. In addition to the lung cancer-related genes (TP53, EGFR, KRAS, PIK3CA, and ROS1), this study revealed "novel" genes not previously implicated in NSCLC. Especially, matrix-remodeling associated 5 was the second most frequently mutated gene in NSCLC (first is TP53). Subsequent Sanger sequencing of matrix-remodeling associated 5 in an additional sample set consisting of 52 paired tumor-normal DNA samples revealed that 15% of Chinese NSCLCs contained somatic mutations in matrix-remodeling associated 5. These findings, together with the results from pathway analysis, strongly indicate that altered extracellular matrix-remodeling may be involved in the etiology of NSCLC.
摘要
在中国，肺癌已成为恶性肿瘤中的头号杀手，与体细胞遗传改变显著相关。我们对 14 例来自中国患者的非小细胞肺癌（NSCLC）与其配对的正常肺组织进行了外显子组测序。除了与肺癌相关的基因（TP53、EGFR、KRAS、PIK3CA 和 ROS1）外，本研究还揭示了以前未涉及 NSCLC 的“新”基因。特别是，基质重塑相关 5 是 NSCLC 中第二常见突变的基因（第一是 TP53）。随后对另外一组由 52 对肿瘤-正常 DNA 样本组成的样本集进行基质重塑相关 5 的 Sanger 测序，结果显示 15%的中国 NSCLC 存在基质重塑相关 5 的体细胞突变。这些发现，加上通路分析的结果，强烈表明细胞外基质重塑的改变可能参与了 NSCLC 的发病机制。
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