title: Metachronous pancreatic cancer originating from disseminated founder pancreatic intraductal neoplasias (PanINs).
abstract: 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.
authors: Department of Surgery Asahikawa Medical University Asahikawa Japan.
authors: Koji
authors: K
authors: Imai
authors: Laboratory of Clinical Bioinformatics Center for Clinical and Biomedical Research, Sapporo Higashi Tokushukai Hospital Sapporo Japan.
authors: Hidenori
authors: H
authors: Karasaki
authors: Laboratory of Clinical Bioinformatics Center for Clinical and Biomedical Research, Sapporo Higashi Tokushukai Hospital Sapporo Japan.
authors: Yusuke
authors: Y
authors: Ono
authors: Department of Medicine Asahikawa Medical University Asahikawa Japan.
authors: Junpei
authors: J
authors: Sasajima
authors: Center for Advanced Research and Education, Asahikawa Medical University Asahikawa Japan.
authors: Shin-Ichi
authors: S
authors: Chiba
authors: Center for Advanced Research and Education, Asahikawa Medical University Asahikawa Japan.
authors: Hiroshi
authors: H
authors: Funakoshi
authors: Life Technologies Japan Tokyo Japan.
authors: Miho
authors: M
authors: Muraki
authors: Life Technologies Japan Tokyo Japan.
authors: Hideki
authors: H
authors: Hanaoka
authors: Life Technologies Japan Tokyo Japan.
authors: Takahisa
authors: T
authors: Furukawa
authors: Department of Surgery Asahikawa Medical University Asahikawa Japan.
authors: Hiroyuki
authors: H
authors: Furukawa
authors: Laboratory of Clinical Bioinformatics Center for Clinical and Biomedical Research, Sapporo Higashi Tokushukai Hospital Sapporo Japan.
authors: Toru
authors: T
authors: Kono
authors: Laboratory of Clinical Bioinformatics Center for Clinical and Biomedical Research, Sapporo Higashi Tokushukai Hospital Sapporo Japan.
authors: Kazuo
authors: K
authors: Nagashima
authors: Laboratory of Clinical BioinformaticsCenter for Clinical and Biomedical Research, Sapporo Higashi Tokushukai HospitalSapporoJapan; Center for Cancer Research, Massachusetts General Hospital and Harvard Medical SchoolBostonMA, USA.
authors: Yusuke
authors: Y
authors: Mizukami
keywords: early dissemination; metachronous pancreatic cancer; next‐generation sequencing; pancreatic intraepithelial neoplasia