Mutation profile of Tibetan lung cancer revealed by whole exome sequencing

Abstract

Abstract Background Lung cancer incidence and mortality could be influenced by altitude. In Tibet population Lung cancer was reported to be the sixth deadly malignant cancer, compared with the first deadly tumor in mainland of China. This study is conducted to investigate the mutation profile of Tibet non-small cell lung cancer by whole-exome sequencing. Methods We enrolled 17 Tibetan lung cancer patients. Composing of seven adenocarcinomas (Tibetan-LUAD) and 10 squamous carcinomas (Tibetan-LUSC). Paired tissues from malignant tumors and normal lymph nodes were subjected to whole exome sequencing by Illumina X TEN platform using paired-end 150X strategy. Results Tibetan LUAD harbored less somatic mutations comparing to median number of somatic mutations detected in TCGA. EGFR mutated most frequently in Tibetan LUAD, but TP53 only mutated in two patients, one of which harbored EGFR mutation as well suggesting reduced responsiveness to first line EGFR-TKIs. Mutation burden of Tibetan-LUSC was similar with TCGA LUSC cohort. In Tibetan LUSC, eight patients carried TP53 mutations. Besides, C>A transversion ratio was lower in Tibetan population than in TCGA for both adenocarcinomas and squamous carcinomas. Mutational signature 1 and 4, which were defined in COSMIC to be related with aging and smoking, contributed largely in Tibetan NSCLC. Other mutational signatures related with failure of DNA double-strand break-repair by homologous recombination and AID/APOBEC cytidine deaminases activation were also noticed. In Tibetan LUAD, amplification in 18 cytobands with q value Conclusions We revealed different mutational landscape, including base substitution status, mutational signature, frequently mutated genes, between Tibetan NSCLC, Chinese Han NSCLC and TCGA NSCLC and provide some insights about the possible role of high-altitude environment on NSCLC and uncovered potential candidate genes for further investigation. Legal entity responsible for the study Guowei Che. Funding Genetron Health (Beijing) Co. Ltd., Beijing, China. Disclosure All authors have declared no conflicts of interest.