Ohwada M, Suzuki M, Saga Y, Suzuki T, Ikeda M, Yamada M, Sato I
Department of Obstetrics and Gynecology, Jichi Medical School, Minamikawachi, Tochigi 329-0498, Japan.
Oncol Rep. 2000 Jul-Aug;7(4):789-92.
To clarify how microsatellite instability (MI) is involved in carcinogenesis of sporadic endometrial carcinoma, we examined mutations of the transforming growth factor beta receptor type II (TGF beta RII) gene in 32 patients with MI-positive sporadic endometrial carcinoma. Moreover, mutations of 4 DNA mismatch repair (MMR) genes (hPMS1, hPMS2, hMLH1, hMSH2), which are considered to cause MI, were investigated as well. With respect to the TGF beta RII gene, mutations in the 10-bp polyadenine repeat sequence were observed in 7 of 29 informative cases (24%). Concerning MMR genes, a T to C point mutation at the -6 intronic splice acceptor site of exon 13 of hMSH2 was detected in 43% (6/14). However, there was no mutation in any exon of these 4 MMR genes. These results suggest that there is a carcinogenic mechanism via mutation of the TGF beta RII gene in some cases of MI-positive sporadic endometrial carcinoma. It seems unlikely that the unknown MMR genes are responsible for MI. The implication of the mutation at the intronic splice acceptor site in hMSH2 remains to be clarified.
为阐明微卫星不稳定性（MI）如何参与散发性子宫内膜癌的致癌过程，我们检测了32例MI阳性散发性子宫内膜癌患者的转化生长因子βⅡ型受体（TGFβRII）基因的突变情况。此外，还研究了被认为可导致MI的4种DNA错配修复（MMR）基因（hPMS1、hPMS2、hMLH1、hMSH2）的突变情况。在TGFβRII基因方面，29例信息充分的病例中有7例（24%）在10个碱基对的多聚腺嘌呤重复序列中观察到突变。关于MMR基因，在hMSH2第13外显子的-6内含子剪接受体位点检测到T到C的点突变，发生率为43%（6/14）。然而，这4种MMR基因的任何外显子均未发现突变。这些结果表明，在某些MI阳性散发性子宫内膜癌病例中，存在通过TGFβRII基因突变的致癌机制。未知的MMR基因似乎不太可能是MI的原因。hMSH2内含子剪接受体位点突变的意义仍有待阐明。
