Abstract
Recent studies on small series of pancreatic cancer (PC) with foci of pancreatic intraepithelial neoplasia (PanIN), a putative precursor lesion, have shown that multiple K-RAS mutations may coexist in the same neoplastic pancreas. To see whether mutant-K-RAS polyclonality is a common and specific feature of pancreatic carcinogenesis, we investigated a unselected series of periampullary cancers (41 pancreatic, 13 biliary and two ampullary adenocarcinomas). After hemi-nested polymerase chain reaction (PCR), mutations identified with single strand conformation polymorphism (SSCP) were confirmed by allele-specific PCR and sequencing. K-RAS codon 12 was mutated in 34 (83%) pancreatic cancers and in 11 (85%) biliary cancers. Multiple distinct K-RAS mutations were found in 16 PC (39% of all cases, 47% of those with mutated K-RAS) and in eight biliary cancers (62 and 72%, respectively). In PC, multiple K-RAS mutations were more frequent (P<0.001) in cancers with (nine of 12, 75%) than in those without detectable PanIN (seven of 29, 24%). Individual precursor lesions of the same neoplastic pancreas were found to harbor distinct mutations. Results show that multiple K-RAS mutations are frequent both in PC with associated PanIN and in biliary cancers, and indicate that clonally distinct precursor lesions of PC might variably contribute to tumor development.
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This work was partially supported by Consiglio Nazionale Ricerche (CNR), grand number 95.02323.CT04.
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Laghi, L., Orbetegli, O., Bianchi, P. et al. Common occurrence of multiple K-RAS mutations in pancreatic cancers with associated precursor lesions and in biliary cancers. Oncogene 21, 4301–4306 (2002). https://doi.org/10.1038/sj.onc.1205533
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DOI: https://doi.org/10.1038/sj.onc.1205533
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