Whole-exome sequencing identifies prognostic mutational signatures in gastric cancer.

Abstract

BackgroundGastric cancer (GC) is a heterogeneous disease, and is a leading cause of cancer deaths in Eastern Asia. Genomic analysis, such as whole-exome sequencing (WES), can help identify key genetic alterations leading to the malignancy and diversity of GC, and may help identify new drug targets.MethodsWe identified genomic alterations in a cohort of 38 GC patients, including 26 metastatic and 12 non-metastatic patients. We analyzed the association between novel gene mutations and copy number variations (CNVs) with tumor metastasis and patient survival.ResultsA number of significantly mutated genes in somatic and germline cells were identified. Among them, ATAD3B somatic mutation, a potential biomarker of immunotherapy in stomach cancers, was associated with better patient survival (P=0.0939) and metastasis (P=0.074). POLE germline variation was correlated with shorter overall survival (OS; P=0.0100). Novel CNVs were also identified and can potentially be used as biomarkers. These included 9p24.1 deletion (P=0.0376) and 16p11.2 amplification (P=0.0066), which were both associated with shorter OS. CNVs of several genes including MMP9, PTPN1, and SS18L1 were found to be significantly related to metastasis (P<0.05).ConclusionsWe characterized the mutational landscape of 38 GC patients and discovered several potential new predictive markers of survival and metastasis in GC.