MED12mutations in leiomyosarcoma and extrauterine leiomyoma

Leiomyoma and leiomyosarcoma share morphological features and smooth muscle differentiation, and both arise most frequently within the uterine corpus of middle-aged women. However, they are considered biologically unrelated tumors due to their disparate clinical, cytogenetic, and molecular features. MED12, the mediator complex subunit 12 gene, has been recently implicated as an oncogene in as many as 70% of sporadic uterine leiomyoma. In the present study, we show MED12hotspot exon 2 mutations in extrauterine leiomyoma (3 of 19 cases) and in leiomyosarcoma (3 of 13 uterine cases). We also show that MED12mutations are found in both primary and metastatic leiomyosarcoma. Immunoblotting studies demonstrated MED12 protein expression in 100% of leiomyomas (13) and leiomyosarcomas (20), irrespective of MED12exon 2 mutation status or histological grade. These findings indicate that MED12has oncogenic roles in a broad range of smooth muscle neoplasia, including tumors arising in extrauterine locations.