The study of MED12 gene mutations in uterine leiomyomas from Iranian patients
- 236 Downloads
Uterine leiomyomas are the most common gynecologic benign tumors of the female genital tract that cause a variety of health problems including, abnormal menstrual bleeding, pelvic pain, placenta displacement, premature labor, and miscarriages. Recently, studies showed that recurrent somatic mutations in MED12 exon 2 are the major cause of uterine leiomyomas in different ethnic groups. In order to validate these results in Iranian population, we performed mutational analysis of exon 2 and the flanking intronic regions by using single-strand conformational polymorphism (SSCP) and sequencing analyses in a series of 103 uterine leiomyomas samples. MED12 gene was mutated in 31.07 % of the uterine leiomyomas. Mutations were consisted of 20 missense (62.5 %) and 12 in-frame deletion (37.5 %) mutations and were not detected in normal myometrial tissue. Although this is the lowest mutation frequency reported so far, MED12 mutations are associated with fibroid pathogenesis in the studied population. Understanding the molecular mechanisms responsible for the pathogenesis of uterine leiomyoma will play an important role in designing new therapeutic strategies.
KeywordsMED12 gene Mutation Uterine leiomyomas
This study was supported by the Specialized Research Fund from Shahid Beheshti University of Medical Sciences.
Conflicts of interest
- 14.Liechti-Gallati S, Schneider V, Neeser D, Kraemer R. Two buffer PAGE system-based SSCP/HD analysis: a general protocol for rapid and sensitive mutation screening in cystic fibrosis and any other human genetic disease. Eur J Hum Genet. 1999;7(5):590–8. doi: 10.1038/sj.ejhg.5200338.CrossRefPubMedGoogle Scholar
- 18.McGuire MM, Yatsenko A, Hoffner L, Jones M, Surti U, Rajkovic A. Whole exome sequencing in a random sample of North American women with leiomyomas identifies MED12 mutations in majority of uterine leiomyomas. PLoS One. 2012;7(3), e33251. doi: 10.1371/journal.pone.0033251.CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Markowski DN, Nimzyk R, Belge G, Loning T, Helmke BM, Bullerdiek J. Molecular topography of the MED12-deleted region in smooth muscle tumors: a possible link between non-B DNA structures and hypermutability. Mol Cytogenet. 2013;6(1):23. doi: 10.1186/1755-8166-6-23.CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Nataraj AJ, Olivos-Glander I, Kusukawa N, Highsmith Jr WE. Single-strand conformation polymorphism and heteroduplex analysis for gel-based mutation detection. Electrophoresis. 1999;20(6):1177–85. doi: 10.1002/(SICI)1522-2683(19990101)20:6<1177::AID-ELPS1177>3.0.CO;2-2.CrossRefPubMedGoogle Scholar