In fact, we have observed that the K-Ras(V14I) mutation is capable of cooperating with the p16Ink4a/p19Arf and Trp53 tumour suppressors, as well as with other risk factors such as pancreatitis, thereby leading to a higher cancer incidence.
hTERT and telomerase activity were upregulated in pancreatic cancer compared with paired normal tissues and samples of pancreatitis. hTERT expression correlated with telomerase activity (P .05) and in turn correlated positively with hTERT promoter methylation (P .001) and p16 promoter methylation. hTERT transcript expression and telomerase activity both conferred a worse outcome by univariate and multivariate analysis (P .05).
Mutations in p53 or high-level p16(INK4a) promoter methylation occurred in 29 of 36 (80%) patients with cancer, 3 of 24 (13%) controls, and 3 of 22 (13%) with pancreatitis.
Additionally, we analysed the aberrant methylation frequency of cell cycle inhibitor p16(INK4a) and K-ras gene mutations in the pancreatic samples. p16 inactivation was detected in 43% of adenocarcinomas, in 17% of neuroendocrine tumors, in 18% of pancreatitis and in 63% of pancreas cancer cell lines.