Abstract 1161: the Role of MED12 Exon 2 Mutations in Histopathological Variants of Uterine Leiomyoma

Abstract Uterine leiomyomas, or fibroids, are benign tumors affecting millions of women worldwide. They arise from the overgrowth of smooth muscle and connective tissue. Regardless of their benign nature, leiomyomas can cause considerable morbidity, such as abdominal pain, excessive bleeding, pregnancy complications and even infertility. They also pose a considerable socio-economic impact and are the most common cause for hysterectomy. Based on histopathology, uterine leiomyomas can be divided into various subtypes. Cellular, atypical and mitotically active fibroids are examples of relatively rare variants of common leiomyomas. Rarely, fibroids may undergo malignant transformation and develop into a leiomyosarcoma. We recently showed that MED12 (mediator complex subunit 12) exon 2 is mutated in approximately 70% of uterine leiomyomas (ref 1). The mutation hot spot affects an evolutionary conserved region of the MED12 protein. MED12 is part of a 26-subunit protein complex, which is thought to regulate global as well as gene-specific transcription by bridging DNA regulatory elements to the RNA polymerase II initiation complex. To study the frequency of MED12 exon 2 mutations in different histopathological variants of uterine leiomyoma, we analyzed 105 fibroids and 61 leiomyosarcomas by direct sequencing. Both rare histopathological variants and leiomyosarcomas harbored significantly less MED12 exon 2 mutations than common leiomyomas. The driver mutations underlying these lesions remain to be characterized. (1) N Mäkinen et al. (2011) MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science 14, 252-255. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1161. doi:1538-7445.AM2012-1161