Analysis of ras gene mutations in biliary and pancreatic tumors by polymerase chain reaction and direct sequencing

Abstract

Ras gene is one of the oncogenes most commonly detected in human cancers and consists of three families (H-ras, K-ras, N-ras) that are converted to active oncogenes by point mutations occurring in codon 12, 13, or 61. The authors analyzed mutations of these codons in 12 extrahepatic bile duct carcinomas, nine gallbladder carcinomas, and 20 pancreatic tumors (18 pancreatic adenocarcinomas and two islet cell tumors) by a method to directly sequence nucleotides, using polymerase chain reaction and a direct sequencing method. Point mutations at K-ras codon 12 were found in all of 18 pancreatic adenocarcinomas and in one bile duct carcinoma, but there were no mutations in the remaining 11 bile duct carcinomas, in all of 9 gallbladder carcinomas, or in two islet cell tumors. A very high incidence of ras gene mutations may be used clinically for the diagnosis of debatable cases of pancreatic adenocarcinoma.

Determination of pancreatic ductal carcinoma histogenesis by analysis of mucous quality and K-ras mutation

“…15 In previous reports, the frequency of K-ras activaIt is not observed in normal epithelia. 9,15,16 This study tion was especially high in adenomas or adenocarcinorevealed a similar frequency of K-ras mutation: 85% mas arising in several epithelioglandular organs, e.g., in SCs, 65% in DCs, 46% (75/164) in MCH foci of SC in 75 -95% of pancreatic solid-type carcinomas, 6,7,10 -14 cases, 41% (40/98) in MCH foci of DC cases, 18% (9/ 8 -67% of bile duct carcinomas, [26][27][28][29][30][31][32] 0 -60% of pancre-51) in MCH foci in normal pancreata, and zero (0/87) atic ductectatic-type carcinomas, 17,23,24 13 -54% of tuin normal epithelia (Tables 2 -4, 6).…”

“…mors of the papilla of Vater, [32][33][34][35] 26 -50% of colorectal However, to understand the tumorigenic role of tumors, 25,26 0 -50% of lung adenocarcinomas, [37][38][39][40][41] and K-ras mutations in MCH and carcinoma, it is neces-0 -39% of gallbladder carcinomas. 42,43 Several extra sary to study mutation of the K-ras gene in these two conditions have been suggested to have some connectissues isolated from the same case.…”

Vandetanib (ZD6474), an inhibitor of VEGFR and EGFR signalling, as a novel molecular-targeted therapy against cholangiocarcinoma

“…These in vitro results suggest that in cholangiocarcinoma cells, upregulation of the RAS/RAF/MAPK pathway by mutant KRAS might counteract the anti-growth effect of vandetanib by EGFR inhibition. The incidence of KRAS mutation in cholangiocarcinoma is estimated to be 54 -67% (Tada et al, 1990;Tannapfel et al, 2000), and therefore it may be important to examine the KRAS status when evaluating the activity of EGFR inhibitors in cholangiocarcinoma.…”

Beta-catenin mutations in hepatocellular carcinoma correlate with a low rate of loss of heterozygosity

“…However, cellular transformation mechanisms elicited by these etiologic agents remain unclear. The few genetic alterations that were reported in HCC include p53, IGF2R, K-ras, N-ras and RB1 mutations and, on rare occasions, insertional mutagenesis of cellular genes by HBV integration (Bressac et al, 1990;de Souza et al, 1995;Tada et al, 1990;de The et al, 1987;Wang et al, 1990;Graef et al, 1994). Cytogenetic studies (Simon et al, 1990;Bardi et al, 1992), and more recently comparative genomic hybridization and high density allelotypes showed recurrent allelic losses on chromosome 1p, 4q, 6q, 8p, 9p, 13q, 16p, 16q and 17p (Marchio et al, 1997;Boige et al, 1997;Nagai et al, 1997).…”