title: MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas.
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.
authors.affiliation: Department of Medical Genetics, Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland.
authors.forename: Netta
authors.initials: N
authors.lastname: Mäkinen
authors.forename: Miika
authors.initials: M
authors.lastname: Mehine
authors.forename: Jaana
authors.initials: J
authors.lastname: Tolvanen
authors.forename: Eevi
authors.initials: E
authors.lastname: Kaasinen
authors.forename: Yilong
authors.initials: Y
authors.lastname: Li
authors.forename: Heli J
authors.initials: HJ
authors.lastname: Lehtonen
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Gentile
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.forename: Martin
authors.initials: M
authors.lastname: Enge
authors.forename: Minna
authors.initials: M
authors.lastname: Taipale
authors.forename: Mervi
authors.initials: M
authors.lastname: Aavikko
authors.forename: Riku
authors.initials: R
authors.lastname: Katainen
authors.forename: Elina
authors.initials: E
authors.lastname: Virolainen
authors.forename: Tom
authors.initials: T
authors.lastname: Böhling
authors.forename: Taru A
authors.initials: TA
authors.lastname: Koski
authors.forename: Virpi
authors.initials: V
authors.lastname: Launonen
authors.forename: Jari
authors.initials: J
authors.lastname: Sjöberg
authors.forename: Jussi
authors.initials: J
authors.lastname: Taipale
authors.forename: Pia
authors.initials: P
authors.lastname: Vahteristo
authors.forename: Lauri A
authors.initials: LA
authors.lastname: Aaltonen
mesh_terms: D003062:Codon; D005091:Exons; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D054643:INDEL Mutation; D007438:Introns; D007889:Leiomyoma / Q000235:genetics* / Q000378:metabolism; D056892:Mediator Complex / Q000235:genetics*; D009154:Mutation; D020125:Mutation, Missense; D015398:Signal Transduction; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D003062:Codon; C460107:MED12 protein, human; D056892:Mediator Complex