title: MED12 exon 2 mutations in uterine and extrauterine smooth muscle tumors.
abstract: Mutations in exon 2 of the MED12 gene have been reported in 50% to 70% of uterine leiomyomas. To determine the frequency of MED12 mutations in various types of smooth muscle tumors as well as normal uterine myometrium adjacent to a leiomyoma, we selected a total of 143 cases for analysis of MED12 exon 2 mutations by polymerase chain reaction and Sanger sequencing. MED12 mutations were detected in 54% of classical uterine leiomyomas (15/28) and in 15% of cases in myometrium adjacent to leiomyomas (2/13); 34% of leiomyoma/leiomyomatosis in pelvic/retroperitoneal sites (10/29); 0% of extrauterine leiomyomas (0/29); 8% of smooth muscle tumor of uncertain malignant potential (1/12); 30% of uterine leiomyosarcomas (6/20); and 4% of extrauterine leiomyosarcomas (1/25). Mutations were clustered around codons 44, 40, 41, and 36, and consisted primarily of single nucleotide substitutions and small in-frame deletions. Our results confirm the findings of similar recent studies and further show that pelvic and retroperitoneal leiomyomas harbor an increased frequency of MED12 mutations (34%) as compared with other extrauterine sites (0%; P = 0.0006), and that histologically unremarkable adjacent myometrium can harbor similar MED12 mutations. These findings suggest that smooth muscle tumors in pelvic/retroperitoneal sites are subject to the same mutational changes as those of uterine myometrium, and that these mutations may precede the gross or histological development of a leiomyoma.
authors.affiliation: Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Schwetye
authors.forename: John D
authors.initials: JD
authors.lastname: Pfeifer
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Duncavage
mesh_terms: D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000235:genetics* / Q000473:pathology; D018231:Leiomyomatosis / Q000235:genetics / Q000473:pathology; D007890:Leiomyosarcoma / Q000235:genetics*; D056892:Mediator Complex / Q000235:genetics*; D009154:Mutation; D009215:Myometrium / Q000378:metabolism; D012186:Retroperitoneal Neoplasms / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018235:Smooth Muscle Tumor / Q000235:genetics* / Q000473:pathology; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C460107:MED12 protein, human; D056892:Mediator Complex
keywords: Leiomyoma; Leiomyosarcoma; MED12; Smooth muscle