4735 - Mutation profile of Tibetan lung cancer revealed by Whole Exome Sequencing

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< 0.25 were remarked. Deletions in two cytoband regions (17p13.1 and 19q13.41) were detected and the q value were 0.025 and 0.056 respectively. For Tibetan-LUSC, amplifications in 22 cytoband regions were remarked with q value <0.25 and deletions were detected in eight cytoband regions with q value between 0.001 and 0.25.

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.

Clinical trial identification

Editorial acknowledgement

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.