Molecular diagnosis of pancreatic cancer

Pancreatic ductal adenocarcinoma is a result of accumulated genetic alterat ions, including oncogenes such as K-ras, tumor-suppressor genes such as p53 , p16 and DPC4 and genome-maintenance genes such as BRCA2, microsatellite i nstability and telomerase. Recent findings which characterize the molecular genetic profile of the pancreatic cancer have reshaped the nomenclature de scribing histological progression in pancreatic ductal tumorigenesis. Kras mutations frequently occur early, whereas changes in the expression and gen etic integrity of the p16 gene appear in intermediate lesions, and the inac tivation of the p53, DPC4 genes and activation of telomerase occur late in the neoplastic progression. So far K-ras and telomerase activity have been used as molecular markers for the diagnosis of pancreatic carcinoma, wherea s p53 and p16 may be a prognostic indicator of pancreatic cancer. Additiona l tumor-suppressor genes and the related signaling pathway such as ALK-5 ar e likely to be defined. In addition to the human genome project, these new advances hopefully will accelerate the development of diagnostic and screen ing techniques for this grave condition.