Datta Sayantan, Chattopadhyay Esita, Ray Jay Gopal, Majumder Mousumi, Roy Puspita Das, Roy Bidyut
Human Genetics Unit, Indian Statistical Institute, 203 B.T. Road, Kolkata, 700108, India.
Tumour Biol. 2015 Apr;36(4):3025-33. doi: 10.1007/s13277-014-2937-2. Epub 2014 Dec 20.
Apart from genomic DNA, mutations at mitochondrial DNA (mtDNA) have been hypothesized to play vital roles in cancer development. In this study, ∼5 kb deletion and D-loop mutations in mtDNA and alteration in mtDNA content were investigated in buccal smears from 104 healthy controls and 74 leukoplakia and 117 cancer tissue samples using Taqman-based quantitative assay and re-sequencing. The ∼5 kb deletion in mtDNA was significantly less (9.8 and 10.5 folds, P < 0.0001) in cancer tissues compared to control and leukoplakia tissues, respectively. On the other hand, somatic mutations in D-loop, investigated in 54 controls, 50 leukoplakias and 56 cancer patients, were found to be significantly more in cancer tissues, but not in leukoplakia tissues, compared to control (Z-score = 5.4). MtDNA contents were observed to be significantly more in leukoplakia (2.1 folds, P = 0.004) and cancer (1.6 folds, P = 0.03) tissues compared to control tissues. So, D-loop somatic mutations and ∼5 kb deletion patterns could be used as distinguishing markers between precancer and cancer tissues. This observation further suggests that somatic mutations in D-loop may facilitate carcinogenesis and cancer cells with less ∼5 kb deletion, i.e., intact mtDNA, may become resistant to apoptosis.
除了基因组DNA外，线粒体DNA（mtDNA）突变被认为在癌症发展中起着至关重要的作用。在本研究中，使用基于Taqman的定量分析和重测序技术，对104例健康对照、74例白斑和117例癌症组织样本的口腔涂片进行了研究，以检测mtDNA中约5 kb的缺失、D环突变以及mtDNA含量的变化。与对照组织和白斑组织相比，癌症组织中mtDNA约5 kb的缺失分别显著减少（9.8倍和10.5倍，P < 0.0001）。另一方面，在54例对照、50例白斑和56例癌症患者中研究的D环体细胞突变，与对照相比，在癌症组织中显著更多，但在白斑组织中没有显著差异（Z分数 = 5.4）。与对照组织相比，白斑组织（2.1倍，P = 0.004）和癌症组织（1.6倍，P = 0.03）中的mtDNA含量显著更高。因此，D环体细胞突变和约5 kb的缺失模式可作为癌前组织和癌症组织之间的鉴别标志物。这一观察结果进一步表明，D环体细胞突变可能促进致癌作用，而约5 kb缺失较少的癌细胞，即完整的mtDNA，可能对凋亡产生抗性。
