Poster Session

P340. Somatic mutations in gene MED 12 among women with the family history of uterine fibroids.

Nelly Sogoyan (RU), Maria Kuznetsova (RU), Victoria Dementyeva (RU), Dmitriy Trofimov (RU), Leila Adamyan (RU)

[Sogoyan] Federal State Institution, Research Center for Obstetrics, Gynecology, and Perinatology named after V.I. Kulakov, Moscow, Russian, [Kuznetsova] Federal State Institution, Research Center for Obstetrics, Gynecology, and Perinatology named after V.I. Kulacov, [Dementyeva ] Federal State Institution, Research Center for Obstetrics, Gynecology, and Perinatology named after V.I. Kulakov, [Trofimov] Federal State Institution, Research Center for Obstetrics, Gynecology, and Perinatology named after V.I. Kulakov, [Adamyan] Federal State Institution, Research Center for Obstetrics, Gynecology, and Perinatology named after V.I. Kulakov

The most significant discovery of recent years about development of uterine fibroids was the description of somatic mutations in a gene called MED12. Objective: To determine the frequency of the occurrence and nature of somatic mutations in exon 2 of the gene MED 12 in 2 groups: Group 1 - women with a first-degree family history of uterine fibroids; Group 2 - with no family history of uterine fibroids. To identify the variability of this exon in different nodes in patients with multiple myomas. Methods: In our research we carried out DNA purification and MED 12 exon 2 amplification, PCR reaction with primers in the segment of MED 12 exon 2 with determination of a sequence of fragments by Sanger sequencing followed by analysis of somatic mutations – single nucleotide replacement and MED 12 exon 2 deletion. Patients: We examined tissues of 167 myomas from 65 patients with uterine myoma, as well as aliquots of blood from every patient. Interventions: Laparoscopic myomectomy or hysterectomy were performed. Tissue samples of the fibroids and an aliquot of the blood of all patients were collected during hysterectomy or myomectomy. DNA extraction and amplification were carried out, the PCR reaction was conducted, and the sequence fragments were identified. Main outcome measures and results: We found that the number of patients with somatic mutations in exon 2 of gene MED 12 was higher in the first group as compared with patients in second group. Thus, the proportion of patients with mutations from the 1st group amounted to 68 % (24 patients out of 35), the proportion of myomatous nodules with mutations totaled 63% (60 nodules out of 95). In the 2nd group the proportion of patients with mutations amounted to 66% (20 patients out of 30), while the proportion of myomatous nodules was of 48% (35 nodules out of 72 samples). Among patients from both groups with multiple myoma mutations were detected in 77% of women, while in 63 % of the patients mutations in the nodes were different. Only in 16 (37 %) patients with multiple fibroids mutations in the nodes were uniform. Conclusion: Our data indicate a possible relationship between the occurrence of somatic mutations in exon 2 of the gene MED 12 and a first-degree family history of uterine fibroids. Detection of different types of mutations in several nodes in patients with multiple fibroids proves that each of these nodes has arisen independently from the cell-predecessor with a unique somatic mutation

 

 

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