Banno Kouji, Susumu Nobuyuki, Hirao Takeshi, Yanokura Megumi, Hirasawa Akira, Aoki Daisuke, Udagawa Yasuhiro, Sugano Kokichi, Nozawa Shiro
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
Cancer Genet Cytogenet. 2003 Oct 1;146(1):58-65. doi: 10.1016/s0165-4608(03)00157-2.
Endometrial cancer is the second most common malignancy in patients with hereditary nonpolyposis colorectal cancer (HNPCC). This cancer is caused by germline mutations in one of the DNA mismatch repair (MMR) genes. The present study was undertaken to analyze the relation between microsatellite instability (MSI) and germline mutations of MMR genes. We analyzed MSI in 38 cases of endometrial cancer. MSI was present in one or more (out of 5 examined) regions in 11 (29%) cases. Furthermore, alterations in MLH1 and MSH2, two culprit genes representative of HNPCC, were examined in the 11 MSI-positive patients using polymerase chain reaction-single-strand conformation polymorphism and sequencing. Germline mutations, namely, 1) a missense mutation at codon 688 (ATG-->ATA, Met-->Ile) and 2) a missense mutation at codon 390 (CTT-->TTT, Leu-->Phe) of the MSH2 gene, were found in 2 of the 11 patients (18%). Although these two cases do not fulfill the new Amsterdam criteria, they had strong family histories of colorectal and endometrial carcinoma. Our results show that genetic testing is important in cases of endometrial cancer with a history suggestive of HNPCC even if the new Amsterdam criteria are not fulfilled.
子宫内膜癌是遗传性非息肉病性结直肠癌（HNPCC）患者中第二常见的恶性肿瘤。这种癌症是由DNA错配修复（MMR）基因之一的种系突变引起的。本研究旨在分析微卫星不稳定性（MSI）与MMR基因种系突变之间的关系。我们分析了38例子宫内膜癌患者的MSI。11例（29%）患者在1个或更多（共检测5个）区域存在MSI。此外，使用聚合酶链反应-单链构象多态性和测序技术，对11例MSI阳性患者检测了HNPCC的两个代表性致病基因MLH1和MSH2的改变。在11例患者中的2例（18%）发现了种系突变，即1）MSH2基因第688密码子（ATG→ATA，Met→Ile）的错义突变和2）第390密码子（CTT→TTT，Leu→Phe）的错义突变。虽然这两例不符合新阿姆斯特丹标准，但它们有结直肠癌和子宫内膜癌的强烈家族史。我们的结果表明，即使不符合新阿姆斯特丹标准，对于有HNPCC病史提示的子宫内膜癌病例，基因检测也很重要。
