Shaik Noor Ahmad, Lone Waseem Gul, Khan Imran Ali, Vaidya Sireesha, Rao Kaipa Prabhakar, Kodati Vijaya Lakshmi, Hasan Qurratulain
Department of Genetics and Molecular Medicine, Vasavi Medical and Research Centre, Hyderabad, India.
Genet Test Mol Biomarkers. 2011 Jul-Aug;15(7-8):537-41. doi: 10.1089/gtmb.2010.0255. Epub 2011 Mar 31.
To identify the role of mitochondrial DNA (mtDNA) mutations in uterine fibroids patients, genomic DNA isolated from paired myometrium and fibroid tissues was screened for mutations. The present study represents the first investigation to report that 10.4% of uterine fibroids cases had either mtDNA mutations or polymorphisms or both. Among the 14 mitochondrial sequence variants identified, seven are somatic mutations (A3327C, G3352A, G3376A, G3380A, G3421A, T15312G, and C15493G) and the remaining (G3316A, C3342A, C3442T, T10205A, A10188G, A10229C, and A10301T) are gene polymorphisms. Somatic mutations were both homo- and heteroplasmic in nature. Of the seven somatic mutations located in the MTND1 and MTCYB genes, five (71.42%) are nonsynonymous in nature, whereas four (57.14%) of the polymorphisms located in MTND1 and MTND3 genes are found to be nonsynonymous. Sequence variants such as G3380A, G3421A, T15312G, G3376A, and G3316A have been earlier described in different human pathologies, but the remaining are novel ones. Mitochondrial somatic mutations and polymorphisms may predispose women to an earlier onset of degenerative cellular processes, which impair oxidative phosphorylation capacity and thereby promote tumorigenesis in uterine smooth muscle cells. Detection of mtDNA sequence variations in fibroid patients raises the need for larger case-control studies to screen the whole mitochondrial genome and evaluate as a future diagnostic biomarker in fibroid patients.
为了确定线粒体DNA（mtDNA）突变在子宫肌瘤患者中的作用，对从配对的子宫肌层和肌瘤组织中分离出的基因组DNA进行了突变筛查。本研究是首次报告10.4%的子宫肌瘤病例存在mtDNA突变或多态性或两者皆有的调查。在鉴定出的14个线粒体序列变异中，7个是体细胞突变（A3327C、G3352A、G3376A、G3380A、G3421A、T15312G和C15493G），其余的（G3316A、C3342A、C3442T、T10205A、A10188G、A10229C和A10301T）是基因多态性。体细胞突变在本质上既有同质性的也有异质性的。在位于MTND1和MTCYB基因中的7个体细胞突变中，5个（71.42%）在本质上是非同义的，而位于MTND1和MTND3基因中的4个（57.14%）多态性被发现是非同义的。诸如G3380A、G3421A、T15312G、G3376A和G3316A等序列变异在不同的人类病理学中已有报道，但其余的是新发现的。线粒体体细胞突变和多态性可能使女性更容易过早发生退行性细胞过程，这会损害氧化磷酸化能力，从而促进子宫平滑肌细胞中的肿瘤发生。检测肌瘤患者中的mtDNA序列变异增加了进行更大规模病例对照研究以筛查整个线粒体基因组并评估其作为肌瘤患者未来诊断生物标志物的必要性。
