Common occurrence of multiple K-RAS mutations in pancreatic cancers with associated precursor lesions and in biliary cancers View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2002-06

AUTHORS

Luigi Laghi, Ombretta Orbetegli, Paolo Bianchi, Alessandro Zerbi, Valerio Di Carlo, C Richard Boland, Alberto Malesci

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. More... »

PAGES

1205533

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1205533

DOI

http://dx.doi.org/10.1038/sj.onc.1205533

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1032131297

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12082617


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