Abstract
The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including the most commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scale sequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma.
Highlights
The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized
In an addition to a number of previously reported lung cancer driver genes, we have identified several novel, potentially oncogenic genes that are significantly mutated in our cohort
We carried out a comprehensive genetic characterization of 335 lung adenocarcinomas by integrating whole-genome sequencing (WGS), Whole-exome sequencing (WES) and RNA-seq
Summary
The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Previous studies have characterized the genomic landscape of lung adenocarcinomas and identified many potential cancer driver genes[4,9,10,11], of which targeting therapies have been developed for several activated oncogenes such as EGFR, ERBB2 and BRAF6,12–14 and translocations or fusions involving ALK, ROS1 and RET15–17. Most of these studies, mainly focused on tumour samples obtained from European or North American patients, and the majority of specimens were collected at early disease stages. These results provide new insights on the pathogenesis of lung adenocarcinomas and form a basis for further improvement of clinical management of our patients in the precision medicine era
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