Mutational analysis of the CTNNB1 and APC genes in uterine endometrioid carcinoma

Despite recent studies, the molecular genetic events responsible for the de velopment of uterine endometrioid carcinoma (UEC) remain incompletely chara cterized Mutations in the beta -catenin (CTNNB1) gene have been recently re ported in a small percentage of UECs and in the endometrioid variant of ova rian carcinoma suggesting that the Wnt signal transduction pathway is invol ved in the development of female genital tract tumors with endometrioid mor phology, The Wnt pathway is a critical pathway in the development of colore ctal cancer (CRC) with mutations occurring in the beta -catenin (CTNNB1) or adenomatous polyposis coli (APO genes in 10 to 15% and 85% of cases, respe ctively. Because UEC and CRC share other molecular genetic alterations and histologic features and previous studies of UEC have not reported an analys is of the APC gene, we chose to further elucidate the role of the Wnt pathw ay in UEC, To this end, we analyzed 32 cases of UEC for mutations of the CT NNB1 and APC genes. Mutations of CTNNB1 were present in six of 32 (18%) cas es: four grade 1 carcinomas, one grade 2, and one grade 3 carcinoma. Five m issense mutations were identified, three involving Ser/Thr phosphorylation sites and two adjacent to a Ser phosphorylation site. One case contained a deletion encompassing codons 34 to 37, which includes a Ser phosphorylation site. No mutations resulting in truncation of the APC protein were found. Our results support a role for the Wnt signaling pathway via mutation of CT NNB1, but not APC, in the development of a subset of UECs.