Genetic alterations in pancreatic carcinoma.
Cancer of the exocrine pancreas represents the fifth leading cause of cancer death in the Western population with an average survival after diagnosis of 3 to 6 months and a five-year survival rate under 5%. Our understanding of the molecular carcinogenesis has improved in the last few years due to the development of novel molecular biological techniques. Pancreatic cancer is a multi-stage process resulting from the accumulation of genetic changes in the somatic DNA of normal cells. In this article we describe major genetic alterations of pancreatic cancer, mutations in the proto-oncogene K-RAS and the tumor suppressors INK4A, TP53 and DPC4/SMAD4. The accumulation of these genetic changes leads to a profound disturbance in cell cycle regulation and continuous growth. The knowledge of the underlying molecular mechanisms will offer new therapeutic and diagnostic options and hopefully improve the outcome of this aggressive disease.
Schneider
Gunter
G
Klinikum rechts der Isar, II. Department of Internal Medicine, Ismaningerstr. 22, D-81675 Munich, Germany. guenter.schneider@lrz.tum.de
Schmid
Roland M
RM
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D016193:G1 Phase / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D000090063:Proto-Oncogene Mas; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53