multiregion sequencing of gastric adenomas

In this study, we performed whole-exome sequencing of five gastric adenomas — three microsatellite stable (MSS) and two microsatellite instability-high cases (MSI-H) — each of which was profiled for three regional biopsies and matched normal genomes. The sequencing data was used to identify somatic mutations of single base substitutions or SNV, short insertions/deletions or indels and microsatellite instability (MSI), as well as DNA copy number profiling. Our strategy of multiregion sequencing and mutation profiling provided a means to not only measure the level of ITH, but also categorize the mutations according to regional distribution (e.g., those present across all regional biopsies or region-specific mutations as public and private, respectively). Given that such spatial mutation categories largely correspond to the temporal order of their occurrence during the evolution of cancer, the chronological sequence of somatic mutations was inferred for early gastric carcinogenesis.