부산대학교 도서관

Recent identification of somatic MED12mutations in most uterine leiomyomas brings a new venue for the study of the tumorigenesis of leiomyomas. We are particularly interested in the correlation of MED12and HMGA2gene products in leiomyomas and leiomyosarcomas with and without MED12mutations. To address these issues, in this study we examined MED12mutations in a large cohort of usual type leiomyomas (178 cases) and uterine leiomyosarcomas (32 cases). We found that 74.7% (133/178) of leiomyomas had MED12mutations, which was consistent with several independent studies. In contrast, only 9.7% (3/32) of leiomyosarcomas harbored MED12mutations. Expression analysis by western blot and immunohistochemistry revealed that those leiomyomas with complex MED12mutations had significantly lower protein products than the matched myometrium. Interestingly, most leiomyosarcomas without MED12mutations also had very low levels of MED12expression in comparison to the matched myometrium. These findings suggest a potential functional role of MED12in both benign and malignant uterine smooth muscle tumors. When we further examined HMGA2expression in all leiomyomas and leiomyosarcomas, we found that HMGA2overexpression was exclusively present in those leiomyomas with no MED12mutation, accounting for 10.1% (18/178) of total leiomyomas and 40% (18/45) of non-MED12mutant leiomyomas. Twenty-five percent (8/32) of leiomyosarcomas had HMGA2overexpression, and no MED12mutations were found in HMGA2positive leiomyosarcoma. These findings strongly suggest that MED12mutations and HMGA2overexpression are independent genetic events that occur in leiomyomas, and they may act differently in the tumorigenesis of uterine leiomyomas.