K-ras mutation and pancreatic adenocarcinoma

Pancreatic adenocarcinoma, the human tumor with the highest incidence of K-ras mutations, is one of the leading causes of cancer death and has a very poor prognosis. Over the past few years, a molecular genetic profile of pancreatic cancer has started to emerge: K-ras mutations in at least 90% of cases, MTS1 alterations (somatic mutations and homozygous deletions) in 80%, p53 mutations in about 70%, as well as multiple sites of allelic loss in cancer cells. The detection of K-ras mutations is done by using one of several PCR-based methods. A modified allele-specific ligation assay recently described appears particularly simple and reproducible. The possibility of pancreatic ductal lesions being the early precursors of pancreatic cancer has gained support from the finding of frequent K-ras mutations in these lesions. Although K-ras mutations are a defining event in pancreatic ductal carcinogenesis, it is unclear in which genetic context they occur. K-ras mutations as markers of cancer cells have been detected in clinical specimens from patients, including stool and blood, raising the possibility of early diagnosis. In addition K-ras can be a molecular target for therapeutic intervention, as illustrated with the use of farnesylation inhibitors.