MED12, the Mediator Complex Subunit 12 Gene, Is Mutated at High Frequency in Uterine Leiomyomas
Menée initialement sur 18 échantillons tumoraux prélevés sur 17 patientes atteintes d'un léiomyome utérin, puis sur 207 échantillons complémentaires, cette étude de séquençage des exons montre que le gène MED12, un régulateur de la transcription, est fréquemment muté
Uterine leiomyomas, or fibroids, are benign tumors that affect millions of women worldwide and that can cause significant 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% (159/225) 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.
Science 2011