Oncogene  2002 Jun 20;21(27):4301-6 

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

Laghi L, Orbetegli O, Bianchi P, Zerbi A, Di Carlo V, Boland CR, Malesci A.

Division of Gastroenterology, Istituto Clinico Humanitas, Rozzano, Milan, 20089
Italy.

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.

PMID: 12082617 [PubMed - indexed for MEDLINE]