1. Integrative and comparative genomic analysis of lung squamous cell carcinomas in East Asian patients.
- Author
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Kim Y, Hammerman PS, Kim J, Yoon JA, Lee Y, Sun JM, Wilkerson MD, Pedamallu CS, Cibulskis K, Yoo YK, Lawrence MS, Stojanov P, Carter SL, McKenna A, Stewart C, Sivachenko AY, Oh IJ, Kim HK, Choi YS, Kim K, Shim YM, Kim KS, Song SY, Na KJ, Choi YL, Hayes DN, Kim J, Cho S, Kim YC, Ahn JS, Ahn MJ, Getz G, Meyerson M, and Park K
- Subjects
- Adult, Aged, Aged, 80 and over, Asian People genetics, Carcinoma, Squamous Cell ethnology, Class I Phosphatidylinositol 3-Kinases, DNA-Binding Proteins genetics, Female, Humans, Intracellular Signaling Peptides and Proteins genetics, Kelch-Like ECH-Associated Protein 1, Lung Neoplasms ethnology, Male, Middle Aged, Models, Genetic, Mutation, NF-E2-Related Factor 2 genetics, Neoplasm Proteins genetics, PTEN Phosphohydrolase genetics, Phosphatidylinositol 3-Kinases genetics, Republic of Korea, Retinoblastoma Protein genetics, Smoking, Tumor Suppressor Protein p53 genetics, United States, White People genetics, Carcinoma, Squamous Cell genetics, Gene Expression Regulation, Neoplastic, Lung Neoplasms genetics, Transcriptome
- Abstract
Purpose: Lung squamous cell carcinoma (SCC) is the second most prevalent type of lung cancer. Currently, no targeted therapeutics are approved for treatment of this cancer, largely because of a lack of systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SCC, we probed somatic genome alterations of lung SCC by using samples from Korean patients., Patients and Methods: We performed whole-exome sequencing of DNA from 104 lung SCC samples from Korean patients and matched normal DNA. In addition, copy-number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated., Results: This cancer cohort is characterized by a high mutational burden with an average of 261 somatic exonic mutations per tumor and a mutational spectrum showing a signature of exposure to cigarette smoke. Seven genes demonstrated statistical enrichment for mutation: TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2, and PIK3CA). Comparative analysis between Korean and North American lung SCC samples demonstrated a similar spectrum of alterations in these two populations in contrast to the differences seen in lung adenocarcinoma. We also uncovered recurrent occurrence of therapeutically actionable FGFR3-TACC3 fusion in lung SCC., Conclusion: These findings provide new steps toward the identification of genomic target candidates for precision medicine in lung SCC, a disease with significant unmet medical needs.
- Published
- 2014
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