[Frontiers in Bioscience 3, d1148-1160, November 15, 1998] |
MOLECULAR PATHOBIOLOGY OF PANCREATIC ADENOCARCINOMA
Shamlal Mangray and Thomas C King
Department of Pathology and Laboratory Medicine, Brown University School of Medicine, Providence, RI
Received 8/24/98 Accepted 9/4/98
Knowledge of the molecular biology of pancreatic adenocarcinoma has grown rapidly and has potential implications for the surgical, radiation, and chemotherapeutic management of this deadly disease. Understanding the genetics of pancreatic adenocarcinoma will become even more important as more effective therapeutic strategies are developed and tested. While all pancreatic adenocarcinomas are not genetically identical, they share many common features with a very high frequency of alterations in K-ras, p53, and p16INK4a genes. The p16INK4a gene and the closely linked p15 and p19 genes appear to be of special significance in that they are more frequently targeted in pancreatic adenocarcinoma than in any other neoplasm. In addition, the genetic predisposition for developing pancreatic adenocarcinoma in the FAMMM syndrome with p16INK4a gene mutations suggests that p16INK4a can be involved in the genesis of these tumors. Other oncogenes and tumor suppressor genes are clearly involved in producing most pancreatic adenocarcinomas so that the genotype of these tumors is quite complex.