Laboratory of Clinical Bioinformatics Center for Clinical and Biomedical Research

Laboratory of, Japan

Laboratory of Clinical Bioinformatics Center for Clinical and Biomedical Research

Laboratory of, Japan

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PubMed | Asahikawa University, Life Technologies, Massachusetts General Hospital and Laboratory of Clinical Bioinformatics Center for Clinical and Biomedical Research
Type: Journal Article | Journal: The journal of pathology. Clinical research | Year: 2016

Clonal populations originated from benign-looking founder cells may spread widely within pancreas instead of being localized in situ before frank pancreatic ductal adenocarcinoma (PDA) can be detected. Metachronous PDA is not common event, and we here sought to define potent origin of multiple PDAs developed in a woman using advanced genetics technologies. Curative resection of pancreatic head tumour was performed; however, recurrent lesions in the remnant pancreas were found 3.5 years later and total pancreatectomy was subsequently performed. The metachronous lesions were morphologically similar to the primary PDA. Using a next-generation sequencing and digital PCR, all three PDAs were shown to possess rare somatic mutations in KRAS (p.T58I & p.Q61H). Curiously, identical KRAS mutations were found in low-grade intraepithelial lesions, which localized in normal area of the pancreas and one of them possessed p53 mutation, which was also found in the PDAs. The footprint of the tumour evolution marked by mutational profiling supports a human correlate to the mouse models of dissemination occurring at the earliest stages of pancreatic neoplasia.

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