Albitar Lina, Al-Chatty Eyad, Ahmad Fariz
Department of Pathology, Faculty of Medicine, Damascus University, Damascus, Syria.
Department of Pathology, National University Hospital, Damascus, Syria.
Sci Rep. 2025 Jan 2;15(1):452. doi: 10.1038/s41598-024-84439-4.
Uterine leiomyomas (uLMs) are the most prevalent benign tumors of the female reproductive system. MED12 is one of the mediator complex subunits that has been implicated in uLMs pathogenesis. Somatic mutations in exon2-MED12 have been found in ~ 70% of uLMs. In this study, we investigated the status of exon2-MED12 in uLMs from Syrian patients. Sixteen leiomyomas from nine patients were assessed. Genomic DNA was isolated from tumors and exon2-MED12 was amplified by PCR and sequenced. Three specimens showed in frame point mutations consisted of missense substitutions in codon 44 (c.130). A novel insertion in codon 35 (c.103insG) was detected in one of the mutated cases and is expected to cause a frameshift in translation and an altered or truncated product. Some of the wild-type uLMs were collected from the same uteri that revealed mutations, which emphasizes the individuality of the uLM lesions and highlights the complexity of uLMs pathogenesis. The study is the first report from Syria on the topic and the second from the Arab world. It indicates genetic heterogeneity and independent clonal origin of the somatic mutations in exon2-MED12. In wild-type uLMs where exon2-MED12 mutations are absent, other players are in place and should be investigated.
子宫平滑肌瘤（uLMs）是女性生殖系统中最常见的良性肿瘤。MED12是中介体复合物亚基之一，与uLMs的发病机制有关。在约70%的uLMs中发现了外显子2-MED12的体细胞突变。在本研究中，我们调查了叙利亚患者uLMs中外显子2-MED12的状态。对9名患者的16个平滑肌瘤进行了评估。从肿瘤中分离基因组DNA，通过PCR扩增外显子2-MED12并进行测序。三个标本显示框内点突变，由密码子44（c.130）的错义替换组成。在其中一个突变病例中检测到密码子35的一个新插入（c.103insG），预计会导致翻译移码并产生改变或截短的产物。一些野生型uLMs是从发现有突变的同一子宫中收集的，这强调了uLM病变的个体性，并突出了uLMs发病机制的复杂性。该研究是叙利亚关于该主题的首次报告，也是阿拉伯世界的第二篇报告。它表明外显子2-MED12体细胞突变的遗传异质性和独立克隆起源。在不存在外显子2-MED12突变的野生型uLMs中，其他因素起作用，应进行研究。
