Analysis of MED12 Mutation in Multiple Uterine Leiomyomas in South Korean patients

Abstract

Uterine leiomyomas are one of the most common benign gynecologic tumors, but the exact causes are not completely understood. In 2011, through DNA sequencing, MED12 mutation was discovered in approximately 71% of uterine leiomyomas. Several recent studies confirmed the high frequency of MED12 mutation in uterine leiomyoma. Nevertheless, no study has been done on MED12 mutation in the case of patients with multiple leiomyomas in a patient. The purpose of this study was to investigate the frequency of MED12 mutations in uterine leiomyomas of South Korean patients. In addition, we examined MED12 mutation in multiple leiomyomas in the same patients.Uterine leiomyoma tissues were obtained from symptomatic women who underwent hysterectomy or myomectomy for medically indicated reasons. We collected 60 uterine leiomyomas from 41 women. Tumor size ranged from 1 to 12cm. Patients' ages ranged from 25 to 55 years with an average of 38.4 years.Of the 60 tumors, 40 (66.67%) displayed MED12 mutation. Among the 41 patients, 14 patients had multiple leiomyomas and we analyzed those multiple leiomyomas. Three of them had the same mutations. Five of them, each leiomyoma had a different mutation. Two of them did not have mutation. Four of them had both mutation-positive and mutation-negative leiomyomas.In conclusion, we confirmed the high frequency of the MED12 mutation in uterine leiomyomas of South Korean patients. We also identified various MED12 mutation status in patients with multiple leiomyomas. This suggests that in a given patient, different tumors may have arisen from different cell origins and therefore it is supposed that occurrence of multiple leiomyoma in a single patient may not be caused by intrauterine metastasis or dissemination.

Vitamins and Uterine Fibroids: Current Data on Pathophysiology and Possible Clinical Relevance

“…All MED12 gene mutations were located within exon 2 and, most probably, they presented the strongest association with UF development [18]. Various studies were conducted in the following years and confirmed these observations [19,20].…”

Transcriptome Analyses of Myometrium from Fibroid Patients Reveals Phenotypic Differences Compared to Non-Diseased Myometrium

“…Moreover, the adjacent tissue of different cancer tumors presented a unique intermediate state between healthy and tumor [ 14 ]. To test our hypothesis, we compared the transcriptome of myometrial samples from non-fibroid patients, with samples from fibroids with the most common fibroid subtype, MED12 mt [ 17 ], and their matching “normal” myometrium and showed that, although the two tissues are clearly more alike than not when compared to fibroid tissues, there is a distinct phenotype for each.…”

Expanded Somatic Mutation Spectrum of MED12 Gene in Uterine Leiomyomas of Saudi Arabian Women

“…Nevertheless, some histopathological characteristics of leiomyosarcomas such as mitotically active cells have also appeared in leiomyoma cases with MED12 mutations, indicating possible transformation of leiomyoma toward malignancy when somatic mutations are accumulated. MED12 mutations are reported not just in benign uterine neoplasms but also in highly aggressive leiomyosarcomas (Markowski et al, 2012; Mäkinen et al, 2014b; Sadeghi et al, 2016; Yoon et al, 2017; Lee et al, 2018). Moreover elevated number of mitoses in leiomyomas may also result from hormonal factors, because these tumors frequently occur in pregnancy, during the secretory phase of the menstrual cycle, and in patients undergoing hormonal therapy (Walker, 2002; Wise et al, 2004; Salama et al, 2006).…”

“…Variety of MED12 mutations including missense, in-frame insertion-deletions, and intrinsic type variations were found in different leiomyoma phenotypes (Mäkinen et al, 2011a,b, 2014a; Halder et al, 2014; Osinovskaya et al, 2016; Sadeghi et al, 2016; Heinonen et al, 2017; Wang et al, 2017). It is of particular interest, to note that all reported mutations were mostly localized to exon 2, underlining its potential contribution in the genesis of uterine leiomyomas (Barbieri et al, 2012; Mäkinen et al, 2013; Schwetye et al, 2014; Osinovskaya et al, 2016; Lee et al, 2018).…”