Genomic variations in paired normal controls for lung adenocarcinomas
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Li-Wei Qu1,*, Bo Zhou1,2,*, Gui-Zhen Wang1, Ying Chen1 and Guang-Biao Zhou1
1Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
2University of the Chinese Academy of Sciences, Beijing 100049, China
*These authors have contributed equally to this work
Guang-Biao Zhou, email: [email protected]
Keywords: lung cancer; genomic variations; counterpart normal control; tobacco smoke
Received: July 29, 2017 Accepted: September 23, 2017 Published: October 24, 2017
Somatic genomic mutations in lung adenocarcinomas (LUADs) have been extensively dissected, but whether the counterpart normal lung tissues that are exposed to ambient air or tobacco smoke as the tumor tissues do, harbor genomic variations, remains unclear. Here, the genome of normal lung tissues and paired tumors of 11 patients with LUAD were sequenced, the genome sequences of counterpart normal controls (CNCs) and tumor tissues of 513 patients were downloaded from TCGA database and analyzed. In the initial screening, genomic alterations were identified in the “normal” lung tissues and verified by Sanger capillary sequencing. In CNCs of TCGA datasets, a mean of 0.2721 exonic variations/Mb and 5.2885 altered genes per sample were uncovered. The C:G→T:A transitions, a signature of tobacco carcinogen N-methyl-N-nitro-N-nitrosoguanidine, were the predominant nucleotide changes in CNCs. 16 genes had a variant rate of more than 2%, and CNC variations in MUC5B, ZXDB, PLIN4, CCDC144NL, CNTNAP3B, and CCDC180 were associated with poor prognosis whereas alterations in CHD3 and KRTAP5-5 were associated with favorable clinical outcome of the patients. This study identified the genomic alterations in CNC samples of LUADs, and further highlighted the DNA damage effect of tobacco on lung epithelial cells.
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