Firdaus Ruqia, Agrawal Prabha, Anagani Manjula, Vijayalakshmi Kodati, Hasan Qurratulain
Department of Genetics and Molecular Medicine, Vasavi Medical and Research Center, Lakdi-ka-pool, Hyderabad, India.
Department of Biotechnology, Hyderabad Science Society, Hyderabad, India.
J Reprod Infertil. 2021 Jul-Sep;22(3):201-209. doi: 10.18502/jri.v22i3.6720.
Uterine leiomyomata (UL), commonly known as uterine fibroids, are benign smooth muscle tumors of the myometrium. They cause pelvic pain, abnormal uterine bleeding, and infertility in women of reproductive age. The ovarian hormone estrogen is the main stimulator for the fibroid growth. The etiology is not yet clearly understood; however, UL are believed to be monoclonal tumors arising from a common progenitor cell. Chromosomal cytogenetic abnormalities have been demonstrated in 40-50% of the fibroids. The most frequent tumor specific genetic alterations in UL were identified in exon-2 of Mediator Complex Subunit 12 (MED-12).
In the present study, twenty-two multiple fibroids were evaluated both from the same uterus and from different uteri, of four women, for somatic mutations in hotspot region of MED-12. The tissue DNA of the UL's was isolated, amplified by PCR visualized on gel and sent for Sanger sequencing.
The results indicate several variants in exon-2 and flanking intronic regions, seven exonic variants and five intronic variants which provide evidence that multiple UL in the same uterus may not be clonal in origin.
This study indicates genetic heterogeneity. UL may not have a clonal origin, these exon-2 variants of MED-12 gene could be involved in UL progression.
子宫平滑肌瘤（UL），通常被称为子宫肌瘤，是子宫肌层的良性平滑肌肿瘤。它们会导致育龄女性出现盆腔疼痛、异常子宫出血和不孕。卵巢激素雌激素是肌瘤生长的主要刺激因素。其病因尚未完全明确；然而，子宫平滑肌瘤被认为是由一个共同的祖细胞产生的单克隆肿瘤。在40%至50%的肌瘤中已证实存在染色体细胞遗传学异常。子宫平滑肌瘤中最常见的肿瘤特异性基因改变在中介体复合物亚基12（MED-12）的外显子2中被发现。
在本研究中，对来自四名女性同一子宫和不同子宫的22个多发性肌瘤进行了MED-12热点区域体细胞突变的评估。分离子宫平滑肌瘤的组织DNA，通过聚合酶链反应（PCR）扩增，在凝胶上可视化，然后送去进行桑格测序。
结果表明在外显子2和侧翼内含子区域有多个变异，七个外显子变异和五个内含子变异，这表明同一子宫内的多个子宫平滑肌瘤可能并非起源于克隆。
本研究表明存在基因异质性。子宫平滑肌瘤可能并非起源于克隆，MED-12基因的这些外显子2变异可能与子宫平滑肌瘤的进展有关。
