総論(4)膵内分泌腫瘍の遺伝子異常

膵内分泌細胞は多発性内分泌腫瘍症1型(MEN 1)の原因遺伝子の異常が初期に起こり，その後，複数の遺伝子異常が重なって腫瘍化すると考えられる．しかし癌遺伝子やp53遺伝子異常の頻度は少なく，また他の腫瘍抑制遺伝子の関与も明らかにされていない．今後，さらに悪性化および転移に関与する遺伝子についても明らかにする必要がある．
トランスジェニックマウスを用いた多段階腫瘍化機構の研究が進み，膵内分泌細胞の腫瘍化に関与する遺伝子の単離や血管新生抑制因子を用いた治療への応用が試みられている．

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 (MEN 1) gene may be an essential step. In contrast to many other tumors, the frequency of activation of oncogenes such as ras, Gsα，and Gi2α 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 tumongenesis.