Genetic basis of pancreatic cancer

Because, in the normal state, cells of the pancreas show a very low rate of proliferation, entering the cell cycle is assumed to be the initial event during tumorigenesis. So-called checkpoints monitor cell cycle progression and guarantee the proper duplication of the entire genome. Loss of one or more checkpoints causes subsequent accumulation of genetic alterations which finally results in cancer. Cancer cells are characterized by unrestricted growth, invasion of adjacent tissue and metastasis. All of these features can be explained in terms of genetic changes and the functional consequence of these changes. Activation of the proto-oncogene K-Ras and inactivation of the tumour suppressor gene loci INK4a, p53 and SMAD4 are characteristic for pancreatic cancer. The progression model of pancreatic cancer proposes that pancreatic intraepithelia neoplasia is the pre-cancerous lesion. A preferred genetic pathway has started to evolve. Germ-line mutations in specific genes are responsible for cases in which there is a familial predisposition to pancreatic cancer.