食管鳞癌的基因组分析确定了与饮酒相关的突变特征和基因组改变。
Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations.
机构信息
Key Laboratory for Environment and Health (Ministry of Education), School of Public Health, Huazhong University of Science and Technology, No. 13 Hangkong Road, Wuhan 430030, China.
Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China.
出版信息
Nat Commun. 2017 May 26;8:15290. doi: 10.1038/ncomms15290.
Approximately half of the world's 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and RNA in 94 Chinese individuals with ESCC. We identify six mutational signatures (E1-E6), and Signature E4 is unique in ESCC linked to alcohol intake and genetic variants in alcohol-metabolizing enzymes. We discover significantly recurrent mutations in 20 protein-coding genes, 4 long non-coding RNAs and 10 untranslational regions. Functional analyses show six genes that have recurrent copy-number variants in three squamous-cell carcinomas (oesophageal, head and neck and lung) significantly promote cancer cell proliferation, migration and invasion. The most frequently affected genes by structural variation are LRP1B and TTC28. The aberrant cell cycle and PI3K-AKT pathways seem critical in ESCC. These results establish a comprehensive genomic landscape of ESCC and provide potential targets for precision treatment and prevention of the cancer.
全球每年新增的 50 万食管鳞状细胞癌 (ESCC) 病例中，约有一半发生在中国。在这里，我们对 94 名中国 ESCC 患者的 DNA 和 RNA 进行了全基因组测序。我们鉴定了六个突变特征（E1-E6），特征 E4 是与饮酒和酒精代谢酶遗传变异相关的 ESCC 所特有的。我们在 20 个蛋白编码基因、4 个长非编码 RNA 和 10 个非翻译区发现了显著的复发性突变。功能分析表明，三个鳞状细胞癌（食管、头颈部和肺）中六个具有复发性拷贝数变异的基因显著促进癌细胞增殖、迁移和侵袭。受结构变异影响最频繁的基因是 LRP1B 和 TTC28。细胞周期和 PI3K-AKT 通路的异常似乎在 ESCC 中至关重要。这些结果建立了 ESCC 的综合基因组图谱，并为癌症的精准治疗和预防提供了潜在的靶点。
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