Journal Article

Mutational landscape of gastric cancer and clinical application of genomic profiling based on target next-generation sequencing

Chang, Xusheng, Nie, Mingming, Jing, Changqing, Yin, Kai, Shang, Liang, Han, Ting, Liu, Zhaorui, Ding, Dan, Meng, Peng, Zhao, Jiangman, Lin, Ling, Cai, Hui, Yang, Junchi, Lu, Zhengmao, Wu, Shouxin, Hu, Xuguang, Wang, Jinshen

2019

Overview

Background Gastric cancer (GC) is a leading cause of cancer deaths, and an increased number of GC patients adopt to next-generation sequencing (NGS) to identify tumor genomic alterations for precision medicine. Methods In this study, we established a hybridization capture-based NGS panel including 612 cancer-associated genes, and collected sequencing data of tumors and matched bloods from 153 gastric cancer patients. We performed comprehensive analysis of these sequencing and clinical data. Results 35 significantly mutated genes were identified such as TP53 , AKAP9 , DRD2 , PTEN , CDH1 , LRP2 et al. Among them, 29 genes were novel significantly mutated genes compared with TCGA study. TP53 is the top frequently mutated gene, and tends to mutate in male (p = 0.025) patients and patients whose tumor located in cardia (p = 0.011). High tumor mutation burden (TMB) gathered in TP53 wild-type tumors (p = 0.045). TMB was also significantly associated with DNA damage repair (DDR) genes genotype (p = 0.047), Lauren classification (p = 1.5e−5), differentiation (1.9e−7), and HER2 status (p = 0.023). 38.31% of gastric cancer patients harbored at least one actionable alteration according to OncoKB database. Conclusions We drew a comprehensive mutational landscape of 153 gastric tumors and demonstrated utility of target next-generation sequencing to guide clinical management.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Biomedical and Life Sciences / Biomedicine / Cancer genetics / Cancer patients / Clinical actionable alterations / Deoxyribonucleic acid / Development and progression / DNA / DNA damage / DNA repair / DNA sequencing / Dopamine D2 receptors / Dopamine receptors / E-cadherin / ErbB-2 protein / Gastric cancer / Gastrointestinal diseases / Gastrointestinal surgery / Gene mutation / Genes / Genetic aspects / Genomes / Genomics / Genotypes / Health aspects / Hybridization / Immunotherapy / LRP2 protein / Lung cancer / Medical bioinformatics / Medical prognosis / Medicine/Public Health / Methods / Mutation / Next-generation sequencing / p53 Protein / Precision medicine / PTEN protein / Quality control / Stomach cancer / Tumor mutation burden / Tumor proteins / Tumors