| [ Summary ] |
Delineation of the genetic events correlating with neoplastic transformation of pancreatic endocrine cells is at an early stage. Nevertheless, the high frequency of allelic loss on chromosome 11q in pancreatic endocrine tumors suggests that inactivation of the multiple endocrine neoplasia type 1 (MEN1) gene may be an essential step. In contrast to many other tumors, the frequency of activation of oncogenes such as ras, Gs-alpha, and Gi2-alpha or inactivation of the p53 gene is low. Because multiple mutations, which accumulate over time, are required to confer a neoplastic phenotype upon a cell, a global search of the genome for allelic loss in human pancreatic endocrine tumors is necessary. A transgenic mouse model demonstrated the feasibility of analyzing the temporal appearance of genetic changes during multistage tumorigenesis. The appearance of allelic loss of mouse chromosome 9 in insulinomas may contribute to the progression from the angiogenic stage to a solid tumor. Nascent tumors can be significantly impaired solely by applying angiogenesis inhibitors. The transgenic mouse models of de novo tumor progression are anticipated to provide more information concerning the mechanisms of tumorigenesis. |