Sharma Himani, Singh Archna, Sharma Chandresh, Jain Sunesh Kumar, Singh Neeta
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India.
Cancer Cell Int. 2005 Dec 16;5:34. doi: 10.1186/1475-2867-5-34.
Mitochondrial DNA (mtDNA) is known for high mutation rates caused by lack of protective histones, inefficient DNA repair systems, and continuous exposure to mutagenic effects of oxygen radicals. Alterations in the non-coding displacement (D) loop of mitochondrial DNA are present in many cancers. It has been suggested that the extent of mitochondrial DNA mutations might be useful in the prognosis of cancer outcome and/or the response to certain therapies. In order to investigate whether a high incidence of mutations exist in mitochondrial DNA of cervical cancer patients, we examined the frequency of mutations in the D-loop region in 19 patients of cervical cancer.
Mutations, often multiple, were detected in 18 of 19 (95%) patients. The presence of mutations correlated with Human Papilloma Virus (HPV) infection in these patients. Mutations were also detected in normal samples and lymphocytes obtained from cervical cancer patients, but their frequency of occurrence was much lower as compared to the cervical cancer tissues.
Our findings indicate that D-loop alterations are frequent in cervical cancers and are possibly caused by HPV infection. There was no association of mtDNA D-loop mutations with the histopathological grade and tumor staging.
线粒体DNA(mtDNA)因缺乏保护性组蛋白、DNA修复系统效率低下以及持续暴露于氧自由基的诱变作用而具有高突变率。线粒体DNA非编码置换(D)环的改变存在于许多癌症中。有人提出,线粒体DNA突变的程度可能有助于癌症预后和/或对某些治疗的反应。为了研究宫颈癌患者的线粒体DNA是否存在高突变率,我们检测了19例宫颈癌患者D环区域的突变频率。
19例患者中有18例(95%)检测到突变,且通常为多个突变。这些患者中突变的存在与人类乳头瘤病毒(HPV)感染相关。在从宫颈癌患者获得的正常样本和淋巴细胞中也检测到了突变,但与宫颈癌组织相比,其发生频率要低得多。
我们的研究结果表明,D环改变在宫颈癌中很常见,可能由HPV感染引起。mtDNA D环突变与组织病理学分级和肿瘤分期无关。