Cover Image

MED12 exon 2 mutations in uterine leiomyoma’s in women patients of Tehran Province of Iran

Ali Reza Ahmadi, Hajar Porrahim, Hajar Moghadasi, Naeimeh Najafi, Azadeh Rakhshan


Uterine leiomyomas or fibroids are benign smooth muscle tumors of myometrial origin; frequently found in reproductive age women. Uterine leiomyomas commonly cause significant symptoms such as anemia resulting from heavy irregular uterine bleeding, Pelvic discomfort, and bowel/bladder dysfunction from pressure. Fibroids have also been associated with infertility and recurrent abortion. Somatic mutations in MED12 exon 2 have recently been reported in uterine leiomyomas. The aim of our study was to see whether MED12 exon 2 mutations occur in uterine leiomyomas of women patients of Tehran Province of Iran. 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 23 cases for analysis of MED12 exon 2 mutations by polymerase chain reaction and Sanger sequencing. We found that 65℅ of classical uterine leiomyomas harbored mutations in exon 2 of the MED12 gene. Twelve of these mutations were located in codon 44 (c.130-132). In addition, one fibroids 0/43% displayed a missense mutation in codon 36 (c.107).We also observed two (0/86) exonic deletion type.


Al-Hendy, A., Salama, S.A., 2006. Catechol-O-methyltransferase polymorphism is associated with increased uterine leiomyoma risk in different ethnic groups. J. Soci. Gynecol. Invest., 13, 136-44.

Canevari, R.A., Pontes, A., Rosa, F.E., Rainho, C.A., Rogatto, S.R., 2005. Independent clonal origin of multiple uterine leiomyomas that was determined by X chromosome inactivation and microsatellite analysis. Am. J. Obstet. Gynecol., 193, 1395 – 1403.

Conaway, R.C., Conaway, J.W., 2011. Function and regulation of the mediator complex. Curr. Opin. Genet. Dev. 21, 225–230.

Cramer, S.F., Patel, A., 1990. The frequency of uterine leiomyomas. Am. J. Clin. Pathol., 94, 435–438.

Di, X., Yu, L., Moore, A.B., Castro, L., Zheng, X., Hermon, T., Dixon, D., 2008. A low concentration of genistein induces estrogen receptor-alpha and insulin-like growth factor-I receptor interactions and proliferation in uterine leiomyoma cells. Hum. Reprod., 23, 1873–1883.

Fauconnier, A., Chapron, C., Babaki-Fard, K., Dubuisson, J.B., 2000. Recurrence of leiomyomata after myomectomy. Hum. Reprod. Update., 6, 595–602.

Flynn, M., Jamison, M., Datta, S., Myers, E., 2006. Health care resource use for uterine fibroid tumors in the United States. Am. J. Obstet. Gynecol., 195, 955-64.

Guarnaccia, M.M., Rein, M.S., 2001. Traditional surgical approaches to uterinefibroids: abdominal myomectomy and hysterectomy. Clin. Obstet. Gynecol., 44, 385–400.

Hennig, Y., Wanschura, S., Deichert, U., Bartnitzke, S., Bullerdiek, J., 1996. Rearrangements of the high mobility group protein family genes and the molecular genetic origin of uterine leiomyomas and endometrial polyps. Mol. Hum. Reprod., 2, 277-83.

Kjerulff, K.H., Langenberg, P., Seidman, J.D., Stolley, P.D., Guzinski, G.M., 1996. Uterine leiomyomas. Racial differences in severity, symptoms and age at diagnosis. J. Reprod. Med., 41, 483-90.

Lethaby, A., Vollenhoven, B., 2005. Fibroids (uterine myomatosis, leiomyomas). Am. Fam. Physician., 71, 1753–1756.

M€akinen, N., Mehine, M., Tolvanen, J., 2011. MED12, the mediator complex subunit 12 gene,is mutated at high frequency in uterine leiomyomas. Sci., 334, 252–5.

Mäkinen, N., Mehine, M., Tolvanen, J., 2011. MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science. 334, 252–55.

Markowski, D.N., Bartnitzke, S., Loning, T., Drieschner, N., Helmke, B.M., Bullerdiek, J., 2012. MED12 mutations in uterine fibroids -- their relationship to cytogenetic subgroups. Int. J. Cancer., 131, 1528-1536.

Marshall, L.M., Spiegelman, D., Barbieri, R.L., Goldman, M.B., Manson, J.E., Colditz, G.A., Willett, W.C., Hunter, D.J., 1997. Variation in the incidence of uterine leiomyoma among premenopausal women by age and race. Obstet. Gynecol., 90, 967-73.

Nilbert, M., Heim, S., 1990. Uterine leiomyoma cytogenetics. Genes Chromosomes Cancer. 2, 3–13.

Parker, W.H., 2007. Etiology, symptomatology, and diagnosis of uterine myomas. Fertil. Steril., 87, 725-36.

Perot, G., Croce, S., Ribeiro, A., 2012. MED12 alterations in both human benign and malignant uterine soft tissue tumors. PLoS One. 7, e40015-e40015.

Rein, M.S., Friedman, A.J., Barbieri, R.L., Pavelka, K., Fletcher, J.A., 1991. Cytogenetic abnormalities in uterine leiomyomata. Obstet. Gynecol., 77, 923–926.

Risheg, H., Graham, J.M.J.R., Clark, R.D., Rogers, R.C., Opitz, J.M., Moeschler, J.B., Peiffer, A.P., May, M., Joseph, S.M., Jones, J.R., Stevenson, R.E., Schwartz, C.E., Friez, M.J., 2007. A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome. Nat. Genet., 39, 451-453.

Schwartz, C.E., Tarpey, P.S., Lubs, H.A., Verloes, A., May, M.M., Risheg, H., Friez, M.J., Futreal, P.A., Edkins, S., Teague, J., Briault, S., Skinner, C., Bauer-Carlin, A., Simensen, R.J., Joseph, S.M., Jones, J.R., Gecz, J., Stratton, M.R., Raymond, F.L., Stevenson, R.E., 2007. The original Lujan syndrome family has a novel missense mutation (p.N1007S) in the MED12 gene. J. Med. Genet., 44, 472-477.

Taatjes, D.J., 2010. The human mediator complex: a versatile, genome-wide regulator of transcription. Trend. Biochem. Sci., 35, 315–322.

Templeman, C., Marshall, S.F., Clarke, C.A., Henderson, K.D., Largent, J., Neuhausen, S., Reynolds, P., Ursin, G., Bernstein, L., 2009. Risk factors for surgically removed fibroids in a large cohort of teachers. Fertility and Sterility. 92, 1436-46.

Velagaleti, G.V., Tonk, V.S., Hakim, N.M., 2010. Fusion of HMGA2 to COG5 in uterine leiomyoma. Cancer Genet Cytogenet. 202, 11-6.

Full Text: PDF


  • There are currently no refbacks.