Whole-exome sequencing to identify novel somatic mutations in squamous cell lung cancers

Zheng,Cui-Xia; Gu,Zhao-Hui; Han,Bing; Zhang,Rong-Xin; Pan,Chun-Ming; Xiang,Yi; Rong,Xia-Jun; Chen,Xia; Li,Qing-Yun; Wan,Huan-Ying

doi:10.3892/ijo.2013.1991

Whole-exome sequencing to identify novel somatic mutations in squamous cell lung cancers

Authors:
- Cui-Xia Zheng
- Zhao-Hui Gu
- Bing Han
- Rong-Xin Zhang
- Chun-Ming Pan
- Yi Xiang
- Xia-Jun Rong
- Xia Chen
- Qing-Yun Li
- Huan-Ying Wan
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Affiliations: Department of Respiration, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China, Shanghai Centre for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China, Department of Endocrinology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200011, P.R. China, Department of Tumor Surgery, the First Hospital Affiliated to Bengbu Medical College, Bengbu 233003, P.R. China, State Key Laboratory of Medical Genomics, Center of Molecular Medicine, Shanghai Institute of Endocrinology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
Published online on: June 25, 2013 https://doi.org/10.3892/ijo.2013.1991
Pages: 755-764

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Abstract

Squamous cell lung cancer is a major histotype of non-small cell lung cancer (NSCLC) that is distinct from lung adenocarcinoma. We used whole-exome sequencing to identify novel non-synonymous somatic mutations in squamous cell lung cancer. We identified 101 single-nucleotide variants (SNVs) including 77 non-synonymous SNVs (67 missense and 10 nonsense mutations) and 11 INDELs causing frameshifts. We also found four SNVs located within splicing sites. We verified 62 of the SNVs (51 missense, 10 nonsense and 1 splicing-site mutation) and 10 of the INDELs as somatic mutations in lung cancer tissue. Sixteen of the mutated genes were also mutated in at least one patient with a different type of lung cancer in the Catalogue of Somatic Mutation in Cancer (COSMIC) database. Four genes (LPHN2, TP53, MYH2 and TGM2) were mutated in approximately 10% of the samples in the COSMIC database. We identified two missense mutations in C10orf137 and MS4A3 that also occurred in other solid-tumor tissues in the COSMIC database. We found another somatic mutation in EP300 that was mutated in 4.2% of the 2,020 solid-tumor samples in the COSMIC database. Taken together, our results implicate TP53, EP300, LPHN2, C10orf137, MYH2, TGM2 and MS4A3 as potential driver genes of squamous cell lung cancer.

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