Asian Cancer Research Group - Gastric Cancer Whole Genome sequencing

Gastric cancer (GC) is the second most common cause of cancer-related deaths. It is known to be a heterogeneous disease with several molecular and histological subtypes. We perform whole-genome sequencing of 49 GCs with diffuse (N=31) and intestinal (N=18) histological subtypes and identify three mutational signatures, impacting TpT, CpG and TpCp[A/T] nucleotides. The diffuse-type GCs show significantly lower clonality and smaller numbers of somatic and structural variants compared to intestinal subtype. We further divide the diffuse-subtype into one with infrequent genetic changes/low clonality and another with relatively higher clonality and mutations impacting TpT dinucleotide. Notably, we discover frequent and exclusive mutations in Ephrins and SLIT/ROBO signaling pathway genes. Overall, this study delivers new insights into the mutational heterogeneity underlying distinct histologic subtypes of GC that could have important implications for future research in the diagnosis and treatment of GC. Note: The publication uses N=49 paired samples comprising of Tumor and matched PBMC but the data deposited here comprises of 50 Tumor and PBMC pairs. Sample object ERS370307 contains normal sample B61 and tumor sample T61 that are not part of the main study. It is referenced in the run object ERR409960, for the files with "GS01289-DNA_F06" in the path. Kindly ignore this sample from any download or analysis.