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.
Informationist Services, Welch Medical Library, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Reprod Sci. 2024 Feb;31(2):291-308. doi: 10.1007/s43032-023-01297-7. Epub 2023 Jul 29.
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.
子宫平滑肌瘤是全世界育龄妇女中最常见的肿瘤。尽管是良性的，但子宫肌瘤会导致严重的发病率，并对受影响妇女的生活质量产生不利影响。中介复合物亚基 12（MED-12）基因外显子 2 中的体细胞突变是与子宫平滑肌瘤最相关的单一基因突变。本综述的目的是评估 MED-12 突变在子宫肌瘤病理生理学中的当前作用，评估不同人群中 MED-12 突变的发生率，并确定在子宫肌瘤中发现的 MED-12 突变的最常见亚型。使用 Pubmed、Embase、Scopus 和 Web of Science 进行了全面检索。评估 MED-12 突变和人类子宫肌瘤的英语语言出版物，无论是实验性的还是临床性的，都被认为是有价值的。我们确定了 380 项研究，其中 23 项被纳入，共包括 1353 名患者和 1872 个肌瘤。在分析的肿瘤总数中，有 1045 个（55.8%）携带 MED-12 突变。在纳入的 23 项研究中，MED-12 突变在肌瘤样本中的频率从 31.1%到 80%不等。最常见的 MED-12 突变类型是影响外显子 2 第 44 位密码子的杂合错义突变，特别是核苷酸 131。研究报告称，MED-12 突变通过增加 AKT 水平并破坏细胞周期蛋白 C-CDK8/19 激酶活性来发挥作用。在全球范围内，子宫肌瘤中 MED-12 突变的总体平均发生率为 55.8%，但在不同国家之间存在很大差异。
