MED12 exon 2 mutations in uterine and extrauterine smooth muscle tumors

• Published in: Human pathology Vol. 45; no. 1; pp. 65 - 70
• Main Authors: Schwetye, Katherine E., Pfeifer, John D., Duncavage, Eric J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2014; Elsevier Limited
• Subjects: DNA Mutational Analysis; Exons - genetics; Female; Humans; Leiomyoma; Leiomyoma - genetics; Leiomyoma - pathology; Leiomyomatosis - genetics; Leiomyomatosis - pathology; Leiomyosarcoma; Leiomyosarcoma - genetics; MED12; Mediator Complex - genetics; Mutation; Myometrium - metabolism; Pathology; Retroperitoneal Neoplasms - genetics; Retroperitoneal Neoplasms - pathology; Reverse Transcriptase Polymerase Chain Reaction; Smooth muscle; Smooth Muscle Tumor - genetics; Smooth Muscle Tumor - pathology; Tumors; Uterine cancer; Uterine Neoplasms - genetics; Uterine Neoplasms - pathology; Women; MED12; Leiomyoma; Smooth muscle; Leiomyosarcoma
• ISSN: 0046-8177; 1532-8392; 1532-8392
• DOI: 10.1016/j.humpath.2013.08.005

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.