Somatic mutations in MED 12 gene exon 2 in women with a single uterine fibroid or multiple ones


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Abstract

Objective. To search for genetic markers for uterine fibroids in order to optimize diagnosis and management tactics in patients and to predict the risk of recurrence. Subjects and methods. Tissue samples from 167 fibroids and blood aliquots from 65 patients were collected. DNA was extracted and MED12 gene exon 2 amplified. Polymerase chain reaction was carried out to determine sequences using the Sanger method. Results. Women with compromised and uncompromised histories showed different somatic mutation ratios in MED12 gene exon 2 and differences in the distribution of mutations when comparing women with a single uterine fibroid or multiple ones. Conclusion. The findings could reveal a possible interaction of a mutation in the gene under study with a compromised history. Somatic mutation saturation in the subgroups of patients with multiple myomatous nodules indicates that multiple uterine fibroids mainly arise from MED 12 gene mutations, which may be less typical for single f ibro ids.

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About the authors

Nelly S. Sogoyan

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: sogoyan.n@mail.ru
resident

Maria V. Kuznetsova

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: mkarja@mail.ru
PhD, research scientist, laboratory of molecular-genetic methods

Alexanda V. Asaturova

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: a_asaturova@oparina4.ru
PhD, pathologist, senior scientific assistant

Leila V. Adamyan

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia; Moscow State University of Medicine and Dentistry

Email: l_adamyan@oparina4.ru
Academician of RAS, MD, PhD, Professor RAS, Honored Master of Science of the Russian Federation, Head Specialist in Obstetrics and Gynecology of Ministry of Healthcare of Russia, Head of the Department of Surgical Gynecology; Head of the Department of Reproductive Medicine and Surgery, Faculty of Postgraduate Education

Dmitry Yu. Trofimov

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

DSci, professor RAS, Head of Laboratory of molecular-genetic methods

References

  1. Адамян Л.В. Миома матки: диагностика, лечение и реабилитация. М.: ФГБУ Научный центр акушерства, гинекологии и перинатологии им. В.И. Кулакова Минздрава России; 2015. 72с.
  2. Сидорова И. С., Унанян А.Л., Коган Е.А., Гуриев Т.Д. Миома матки у больных молодого возраста: клинико-патогенетические особенности. Акушерство, гинекология и репродукция. 2010; 1: 16-20.
  3. Адамян Л.В., Спицын B.A., Андреева E.H. Генетические аспекты гинекологических заболеваний. Руководство для врачей. М.: ГЭОТАР-Медиа; 2008. 215с.
  4. Torres-de la Roche L.A., Becker S., Cezar C., Hermann A., Larbig A., Leicher L. et al. Pathobiology of myomatosis uteri: the underlying knowledge to support our clinical practice. Arch. Gynecol. Obstet. 2017; 296(4): 701-7. doi: 10.1007/ s00404-017-4494-6.
  5. Подзолкова H.M., Колода Ю.А., Коренная В.В., Кайибханова К.Н. Эффективность вспомогательных репродуктивных технологий при миоме матки. М.: ГБОУ ДПО Российская медицинская академия последипломного образования Минздрава России; 2015: 60-4.
  6. Yang Q., Mas A., Diamond M.P., Al-Hendy A. The mechanism and function of epigenetics in uterine leiomyoma development. Reprod. Sci. 2016; 23(2): 163-75.
  7. Ligon A.H., Morton C.C. Leiomyoma: heritability and cytogenetic studies. Hum. Reprod. Update. 2001; 7(1): 8-14.
  8. Zhang K., Wiener H., Aissani B. Admixture mapping of genetic variants for uterine fibroids. J. Hum. Genet. 2015; 60(9): 533-8.
  9. Makinen N., Mehine М., Tolvanen J., Kaasinen E., Li Y., Lehtonen H.J. et al. MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science. 2011; 334(6053): 252-5.
  10. Markowski D.N., Bartnitzke S., Loning Т., Drieschner H., Helmke B., Butte J. MED 12 mutations in uterine fibroids - their relationship to cytogenetic subgroups. Int. J. Cancer. 2012; 131(7): 1528-36. doi: 10.1002/ijc.27424.
  11. McGuire M.M., Yatsenko A., Hoffner L., Jones М., 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.
  12. Heinonen H.R., Pasanen A., Heikinheimo O., Tanskanen Т., Palin K., Tolvanen J. et al. Multiple clinical characteristics separate MED12-mutation-positive and -negative uterine leiomyomas. Sci. Rep. 2017; 7: 1015. doi: 10.1038/s41598-017-01199-0.
  13. Mittal P., Shin Y.H., Yatsenko S.A., Castro C.A., Surti U., Rajkovic A. MED12 gain-of-function mutation causes leiomyomas and genomic instability. J. Clin. Invest. 2015; 125(8): 3280-4.
  14. Осиновская H.C., Иващенко Т.Э., Долинский А.К., Султанов И.Ю., Гимбовская С., Хоффман Э., Беженаръ В.Ф., Баранов B.C. Мутации гена MED-12 в клетках лейомиомы у женщин Северо-Западного региона РФ. Генетика. 2013; 49(12): 1426-31.
  15. Кузнецова M.B., Трофимов Д.Ю., Тихончук Е.Ю., Согоян Н.С., Адамян Л.В., Сухих Г.Т. Молекулярные механизмы патогенеза миомы матки: анализ мутаций гена MED12 в российской популяции. М.; 2016.
  16. Di Tommaso S., Massari S., Malvasi A., Vergara D., Maffia М., Greco М., Tinelli A. Selective genetic analysis of myoma pseudocapsule and potential biological impact on uterine fibroid medical therapy. Expert Opin. Ther. Targets. 2015; 19(1): 7-12. doi: 10.1517/14728222.2014.975793.
  17. Yatsenko S.A., Mittal P., Wood-Trageser M.A., Jones M.W., Surti U., Edwards R.P. et al. Highly heterogeneous genomic landscape of uterine leiomyomas by whole exome sequencing and genome-wide arrays. Fertil. Steril. 2017; 107(2): 457-66. e9.
  18. Osinovskaya N.S., Malysheva O.V., Shved N.Yu., Ivashchenko T.E., Sultanov I.Yu., Efimova O.A., Yarmolinskaya M.I., Bezhenar V.F., Baranov V.S. Frequency and spectrum of MED12 Exon 2 mutations in multiple versus solitary uterine, leiomyomas from Russian patients. Int. J. Gynecol. Pathol. 2016; 35(6): 509-15. doi: 10.1097/PGP.0000000000000255.

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