Metachronous pancreatic cancer originating from disseminated founder pancreatic intraductal neoplasias (PanINs)

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 multipl...

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Bibliographic Details
Published in:The journal of pathology. Clinical research 2015-04, Vol.1 (2), p.76-82
Main Authors: Imai, Koji, Karasaki, Hidenori, Ono, Yusuke, Sasajima, Junpei, Chiba, Shin‐ichi, Funakoshi, Hiroshi, Muraki, Miho, Hanaoka, Hideki, Furukawa, Takahisa, Furukawa, Hiroyuki, Kono, Toru, Nagashima, Kazuo, Mizukami, Yusuke
Format: Article
Language:English
Subjects:
Adenocarcinoma
Animal models
Cancer therapies
Chemotherapy
Deoxyribonucleic acid
DNA
early dissemination
Genes
Genetic testing
Genomes
Medical research
metachronous pancreatic cancer
Metastasis
Mutation
next‐generation sequencing
Original
p53 Protein
Pancreatic cancer
pancreatic intraepithelial neoplasia
Pancreatitis
Patients
Supervision
Tumors
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Summary: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.
ISSN:2056-4538
2056-4538
DOI:10.1002/cjp2.8