MOLECULAR MECHANISMS OF THE PATHOGENESIS OF UTERINE MYOMA: ANALYSIS OF MUTATIONS IN THE MED 12 GENE IN THE RUSSIAN POPULATION


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Abstract

Objective. To determine the spectrum and frequency of various somatic mutations in myoma tissues in the sequence of MED 12 exon 2 and to identify those specific for the Russian population. Material and methods. Tissue samples of 50 myomas from 42 patients (1 to 4 myomatous nodules from each patient) and blood aliquots from all patients were collected. DNA was extracted and MED 12 exon 2 (the total fragment length was 320 bp) was amplified. The sequence of PCR products, which was obtained with the Sanger method, was determined; somatic mutations (single-nucleotide substitutions and deletions in MED 12 exon 2) were then analyzed. Results. Different variants of somatic mutations in MED 12 exon 2 were detected in 25 of the 50 examined myoma tissue samples. The proportion of tumors with mutations was 50% and that of patients whose myomas exhibited somatic mutations was 43%. Among the detected mutations, single-nucleotide substitutions (6 variants) formed 80%; 20% was represented by deletions of different lengths. The frequencies of each single-nucleotide substitution were calculated. The results were compared with data on European and American populations. Conclusion. Somatic mutations in MED 12 exon 2 are shown to be present in 50% of the examined myoma tissue samples. The frequencies of these mutations are generally consistent with those in the previously published studies conducted in other populations. Thus, mutations in the MED12 gene are genetic markers of leiomyomas, the prognostic value of which calls for further study. Three of the five detected deletions and one single-nucleotide substitution are new, possibly specific for the Russian population.

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About the authors

Maria Vladimirovna Kuznetsova

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: mkarja@mail.ru
PhD, research scientist, Laboratory of molecular-genetic methods Moscow 117997, Ac. Oparina str. 4, Russia

Dmitry Yur'evich Trofimov

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

DSci, Professor RAS, Head of Laboratory of molecular-genetic methods Moscow 117997, Ac. Oparina str. 4, Russia

Ekaterina Yur'evna Tikhonchuk

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

PhD-student, Department of Surgical Gynecology Moscow 117997, Ac. Oparina str. 4, Russia

Nelly Serezhaevna Sogoyan

I.M. Sechenov First Mosow State Medical University

Email: sogoyan.n@mail.ru
student Moscow 119991, Malaya Trubetskaya str., 8/2, Russia

Leila Vladimirovna Adamyan

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia; Moscow State University of Medicine and Dentistry; Moscow State University of Medicine and Dentistry

Academician of RAS, MD, PhD, Professor, 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 Moscow 117997, Ac. Oparina str. 4, Russia; Moscow 127473, Delegatskaya str. 20, bld. 1, Russia

Gennady Tikhonovich Sukhikh

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia; I.M. Sechenov First Mosow State Medical University

Academician of RAS, MD, PhD, Professor, Honored Master of Science of the Russian Federation, Head Moscow 117997, Ac. Oparina str. 4, Russia; Moscow 119991, Malaya Trubetskaya str., 8/2, Russia

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