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Genome Sequencing of Gastric Cancer Reveals Diverse Mutational and Pathogen Signatures

ABSTRACT: We leveraged massively parallel sequencing approach to comprehensively characterize the spectrum of somatic mutations and genomic rearrangements in two intestinal-type gastric adenocarcinomas from patients with and without active Helicobacter pylori infections. The tumours exhibited distinct patterns of genomic changes with more than 16,000 somatic substitutions on average, focal amplifications and rearrangements in the non-active infected tumour and a 7-fold enrichment of micro-deletions in the infected tumour. Paired-end sequences from large insert libraries revealed the structure and origins of large amplicons, including one involving the oncogene KRAS. The mutational frequencies of the tumours revealed patterns of H. pylori infection and mutagenesis and a unique exome signature, providing insights into mechanisms that define the mutational landscape of gastric cancer. For the tumour with active infection, we also reconstructed the genome of the pathogenic H. pylori strain from the raw sequence reads, demonstrating the power of whole-genome shotgun sequencing for simultaneously characterizing the tumour and its associated carcinogen genome.

ORGANISM(S): Homo sapiens

PROVIDER: GSE30833 | GEO | 2012/12/05

SECONDARY ACCESSION(S): PRJNA144189

REPOSITORIES: GEO

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