Asian Cancer Research Group - Gastric Cancer Whole Genome sequencing

TEST Gastric carcinoma is one of the major causes of cancer mortality worldwide. We performed whole genome sequencing confirmed by targeted deep sequencing in 49 MSS gastric adenocarcinoma tumor/normal pairs. A median of 9,054 mutation across the genome per tumor (range of 1726-38,328) were identified corresponding to mutation rate of 2.8 per Mb and half of somatic mutations were C>T/G>A transitions. In addition to chromatin remodeling genes, genes involved in axon guidance signaling (Ephrin, SLT, semaphorin and netrin) were significantly mutated. We suggest the potential activation of the axon guidance signaling as a contributor to gastric cancers may have an impact on therapeutic strategies. Tumor purity estimation and clonal analysis showed ARID2, EPHA7, and PCDH9 tumor suppressor genes involve gastric cancer initiation and mutations of FAT4, TGFBR2, APC, CTNND1, ARID1A, CDH1 and PIK3CA involve tumor progression. Whole-genome analysis provided comprehensive profiling beyond exonic mutations. Frequent structural variations and many fusion genes involving MET or PTEN genes were identified. 14 tumors carried nonsynonymous mutations in mtDNA EBV genome related reads were detected in 4 EBV positive cases.