title: MED12 mutations in leiomyosarcoma and extrauterine leiomyoma.
abstract: Leiomyoma and leiomyosarcoma share morphological features and smooth muscle differentiation, and both arise most frequently within the uterine corpus of middle-aged women. However, they are considered biologically unrelated tumors due to their disparate clinical, cytogenetic, and molecular features. MED12, the mediator complex subunit 12 gene, has been recently implicated as an oncogene in as many as 70% of sporadic uterine leiomyoma. In the present study, we show MED12 hotspot exon 2 mutations in extrauterine leiomyoma (3 of 19 cases) and in leiomyosarcoma (3 of 13 uterine cases). We also show that MED12 mutations are found in both primary and metastatic leiomyosarcoma. Immunoblotting studies demonstrated MED12 protein expression in 100% of leiomyomas (13) and leiomyosarcomas (20), irrespective of MED12 exon 2 mutation status or histological grade. These findings indicate that MED12 has oncogenic roles in a broad range of smooth muscle neoplasia, including tumors arising in extrauterine locations.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Gloria
authors.initials: G
authors.lastname: Ravegnini
authors.forename: Adrian
authors.initials: A
authors.lastname: Mariño-Enriquez
authors.forename: Jaime
authors.initials: J
authors.lastname: Slater
authors.forename: Grant
authors.initials: G
authors.lastname: Eilers
authors.forename: Yuexiang
authors.initials: Y
authors.lastname: Wang
authors.forename: Meijun
authors.initials: M
authors.lastname: Zhu
authors.forename: Marisa R
authors.initials: MR
authors.lastname: Nucci
authors.forename: Suzanne
authors.initials: S
authors.lastname: George
authors.forename: Sabrina
authors.initials: S
authors.lastname: Angelini
authors.forename: Chandrajit P
authors.initials: CP
authors.lastname: Raut
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Fletcher
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000235:genetics* / Q000473:pathology; D007890:Leiomyosarcoma / Q000235:genetics* / Q000473:pathology; D008297:Male; D056892:Mediator Complex / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D060888:Real-Time Polymerase Chain Reaction; D018235:Smooth Muscle Tumor / Q000235:genetics* / Q000473:pathology; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C460107:MED12 protein, human; D056892:Mediator Complex