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The Mediator Complex Subunit 12 (MED-12) Gene and Uterine Fibroids: a Systematic Review

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Abstract

Uterine leiomyomas are the most common tumor of reproductive-age women worldwide. Although benign, uterine fibroids cause significant morbidity and adversely impact the quality of life for affected women. Somatic mutations in the exon 2 of the mediator complex subunit 12 (MED-12) gene represent the most common single gene mutation associated with uterine leiomyomas. The objective of this review was to evaluate the current role of MED-12 mutation in the pathophysiology of uterine fibroids, to assess the prevalence of MED-12 mutation among different populations, and to identify the most common subtypes of MED-12 mutations found in uterine fibroids. A comprehensive search was conducted using Pubmed, Embase, Scopus, and the Web of Science. English-language publications that evaluated MED-12 mutation and uterine fibroids in humans, whether experimental or clinical, were considered. We identified 380 studies, of which 23 were included, comprising 1353 patients and 1872 fibroid tumors. Of the total number of tumors analyzed, 1045 (55.8%) harbored a MED-12 mutation. Among the 23 studies included, the frequency of MED-12 mutation varied from 31.1 to 80% in fibroid samples. The most common type of MED-12 mutation was a heterozygous missense mutation affecting codon 44 of exon 2, specifically the nucleotide 131. Studies reported that MED-12 mutation acts by increasing levels of AKT and disrupting the cyclin C-CDK8/19 kinase activity. The overall average prevalence of MED-12 mutation in uterine fibroids was found to be 55.8% across the global population, though the frequency varied greatly among different countries.

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Data Availability

The data that support the findings of this study were derived from the following resources available in the public domain: PubMed, Embase, Scopus, and Web of Science databases.

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Division of Reproductive Sciences & Women’s Health Research, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Research Building, Room 624, Baltimore, MD, 21205, USA

    Isabela Landsteiner Sampaio Amendola, James Segars & Bhuchitra Singh

  2. Informationist Services, Welch Medical Library, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Marcus Spann

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Contributions

ILSA, JS, and BS conceived of the presented idea and supervised the findings of this work. MS designed a detailed list of search terms and elaborated a search strategy for each bibliographic resource. ILSA searched the databases for review articles for the research questions. ILSA interpreted the data and wrote the manuscript with help from JS and BS. All authors discussed the results and contributed to the final manuscript.

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Correspondence to Bhuchitra Singh.

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Amendola, I.L.S., Spann, M., Segars, J. et al. The Mediator Complex Subunit 12 (MED-12) Gene and Uterine Fibroids: a Systematic Review. Reprod. Sci. 31, 291–308 (2024). https://doi.org/10.1007/s43032-023-01297-7

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