MED12 mutation frequency in unselected sporadic uterine leiomyomas

Fertil Steril. 2014 Oct;102(4):1137-42. doi: 10.1016/j.fertnstert.2014.06.040. Epub 2014 Aug 6.

Abstract

Objective: To determine the frequency of mediator complex subunit 12 (MED12) mutations in well-documented, prospectively collected, unselected series of sporadic uterine leiomyomas to better understand the contribution of MED12 mutations in leiomyoma genesis.

Design: Mutation analysis of two prospectively collected sample series.

Setting: Department of gynecology in university hospital and medical genetics research laboratory.

Patient(s): 164 uterine leiomyomas from 28 patients (13 consecutive and 15 unselected patients) undergoing hysterectomy.

Intervention(s): MED12 mutation screening by direct sequencing, and clinical data collection.

Main outcome measure(s): MED12 mutation status and various clinical variables.

Result(s): MED12 mutations were found in 73 (83.0%) of 88 and 65 (85.5%) of 76 of uterine leiomyomas from the consecutive and unselected patient series, respectively. Smaller tumor size and a larger number of tumors correlated with positive MED12 mutation status.

Conclusion(s): The frequency of MED12 mutations in our prospectively collected uterine leiomyoma sets was higher than in previous works. This is in keeping with the concept that MED12 mutation-positive tumors tend to be smaller in size than MED12 mutation-negative tumors. The results highlight the central role of MED12 mutations in uterine leiomyoma genesis.

Keywords: Fibroids; MED12; genetics; uterine leiomyomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • DNA Mutational Analysis
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Testing / methods
  • Hospitals, University
  • Humans
  • Leiomyoma / genetics*
  • Leiomyoma / pathology
  • Leiomyoma / surgery
  • Mediator Complex / genetics*
  • Middle Aged
  • Mutation*
  • Prospective Studies
  • Risk Factors
  • Uterine Neoplasms / genetics*
  • Uterine Neoplasms / pathology
  • Uterine Neoplasms / surgery

Substances

  • MED12 protein, human
  • Mediator Complex