<i>MED12</i> , the <i>Mediator Complex Subunit 12</i> Gene, Is Mutated at High Frequency in Uterine Leiomyomas

TLDR

Uterine leiomyomas are benign tumors affecting millions of women worldwide and causing morbidity, and the Mediator complex—a 26‑subunit transcriptional regulator linking DNA regulatory sequences to RNA polymerase II initiation—plays a key regulatory role. The study aimed to investigate the genetic basis of uterine leiomyomas by exome sequencing 18 tumors from 17 patients, identifying MED12 mutations in 10. Exome sequencing of 18 uterine leiomyomas from 17 patients was performed to detect tumor‑specific MED12 mutations. MED12 is altered in 70% of uterine leiomyomas (159 of 225 tumors from 80 patients), with all mutations confined to exon.

Abstract

Uterine leiomyomas, or fibroids, are benign tumors that affect millions of women worldwide and that can cause considerable morbidity. To study the genetic basis of this tumor type, we examined 18 uterine leiomyomas derived from 17 different patients by exome sequencing and identified tumor-specific mutations in the mediator complex subunit 12 (MED12) gene in 10. Through analysis of 207 additional tumors, we determined that MED12 is altered in 70% (159 of 225) of tumors from a total of 80 patients. The Mediator complex is a 26-subunit transcriptional regulator that bridges DNA regulatory sequences to the RNA polymerase II initiation complex. All mutations resided in exon 2, suggesting that aberrant function of this region of MED12 contributes to tumorigenesis.