Research on constructing a genome analysis database for malignant tumors

Germline pathogenic variants (GPVs) in BRCA1/2 are established cancer predisposition factors; however, their biological and clinical significance in gastric cancer (GC) remain unclear. In particular, the directionality and evolutionary timing of locus-specific loss of heterozygosity (LOH) and their relationships with homologous recombination deficiency (HRD) have not been systematically examined in BRCA1/2-associated GC. We conducted integrative genomic analyses of four GCs from BRCA1/2 GPV carriers using tumour-normal tissue paired whole-exome sequencing and allele-specific copy number profiling. LOH directionality was inferred by integrating the variant allele fraction, tumour purity, and locus-specific copy number. The relative timing of LOH events during tumour evolution was estimated, and HRD was evaluated using genome instability scores and mutational signature analyses.

• Type: Tumor vs. Matched-Normal
• Archive: Japanese Genotype-phenotype Archive (JGA)