TY - JOUR T1 - Hereditary and somatic DNA mismatch repair gene mutations in sporadic endometrial carcinoma JF - Journal of Medical Genetics JO - J Med Genet SP - 461 LP - 466 DO - 10.1136/jmg.38.7.461 VL - 38 IS - 7 AU - Robert B Chadwick AU - Robert E Pyatt AU - Theodore H Niemann AU - Samuel K Richards AU - Cheryl K Johnson AU - Michael W Stevens AU - Julie E Meek AU - Heather Hampel AU - Thomas W Prior AU - Albert de la Chapelle Y1 - 2001/07/01 UR - http://jmg.bmj.com/content/38/7/461.abstract N2 - Editor—Endometrial cancer (EC) is the second most common malignancy in the hereditary non-polyposis colorectal cancer (HNPCC) syndrome.1 In a recent large study, cumulative cancer incidences by the age of 70 in HNPCC mutation carriers were: colorectal 82%, endometrial 60%, gastric 13%, and ovarian 12%.2 Interestingly, in female mutation carriers the incidence of endometrial cancer (60%) exceeded that of colorectal cancer (CRC) (54%), as had been suggested earlier.2 3 Predisposition to HNPCC is the result of germline mutations in the mismatch repair genes.4 Detectable mutations in the two major genes, MLH1 andMSH2, account for some 3% of all colorectal cancers.5 One might therefore assume that a similar proportion of all endometrial cancer patients would have such mutations; however, in a number of studies addressing this question, extremely few germline mutations have been found. Summarising the studies by Katabuchi et al,6Kobayashi et al,7 Limet al,8 Gurinet al,9 and Kowalskiet al,10 only one germline mutation (in MLH1) was found in a total of 352 EC patients (0.3%). In these studies, mutations were sought in all patients whose tumours were microsatellite instability (MSI) positive.Recent reports have suggested that MSH6might account for many endometrial cancers and that families with these mutations show atypical features of HNPCC with endometrial and ovarian cancers outnumbering colorectal cancers.11 12Additionally, MSI, a hallmark of HNPCC, was low in most tumours associated with MSH6 mutations or was preferentially shown by mononucleotide repeats rather than dinucleotide repeats.12-14 Previous studies have reported that 9-25% of sporadic endometrial cancers display microsatellite instability .7 9 15-18 In the majority of cases, this instability arises through hypermethylation of the MLH1promoter region.9 19-21 This epigenetic change results … ER -