MED12 and uterine smooth muscle oncogenesis: State of the art and perspectives

MED12 is a subunit of the multiprotein complex Mediator, an evolutionary-conserved regulator of transcription. Oncogenic mutations in exon 2 of MED12 occur in nearly 70% of uterine leiomyomas, and together with HMGA, represent the most common genetic anomalies in leiomyoma. This mutational anomaly represents a driver mutation. MED12 mutations are restricted to benign smooth muscle tumours (leiomyomas) of the uterus or of the Müllerian system, but decreased protein expression has also been observed in uterine leiomyosarcomas independently of mutational status, suggesting a possible epigenetic mechanism. The discovery of MED12 involvement in leiomyoma genesis has dramatically contributed to increasing our knowledge on leiomyomas, but many questions remain. Here we summarise the current state of knowledge and perspectives on the role of MED12 in the genesis of uterine smooth muscle tumours.