Toure Silly, Mbaye Fatimata, Gueye Mame Diarra, Fall Malick, Dem Ahmadou, Lamy Jean Baptiste, Sembene Mbacké
Department of Maxillofacial Surgery and Stomatology University Hospital Center Aristide le Dantec, Dakar, Senegal.
GENGESPOP Team, Department of Animal Biology, Faculty of Science and Technology, Cheikh Anta Diop University, Dakar, Senegal. Email:
Asian Pac J Cancer Prev. 2019 Jul 1;20(7):2203-2208. doi: 10.31557/APJCP.2019.20.7.2203.
Background: Somatic mutations affecting the mitochondrial DNA (mtDNA) have been frequently observed in human cancers and proposed as important oncological biomarkers. However, the exact mtDNA mutations that is responsible for the pathogenesis of cancer remains unclear. The aim of this study was to investigate somatic mutations in the MT-CYB and D-Loop regions of mitochondrial DNA (mtDNA) in oral cavity cancers from Senegalese patients. Methods: MT-CYB and the D-Loop of mtDNA derived from 45 oral cavity cancer tissues and 21 control blood samples were assessed by PCR and sequencing. The sequences of MT-CYB and the D-Loop from cancerous tissues were compared with control sequences, and sequence differences were recognized as somatic mutations. Results: Overall, 389 somatic mtDNA mutations were identified, most of which (79.43%) were located in the D-Loop region. The majority of base substitution mutations were G-to-A (63.93%) and T-to-C (16.39%) transitions. In the protein-coding MT-CYB gene, 29 missense mutations were observed. The pathogenic mutation load of MT-CYB was 3.11%. Pathogenic mutations were carried by 25% of patients. pArg76Pro (pArg282Pro in rCRS) was novel and was the most common pathogenic mutation observed. Conclusion: These results strongly indicate that mtDNA mutations are a potential marker of oral cavity cancer.
影响线粒体DNA(mtDNA)的体细胞突变在人类癌症中经常被观察到,并被认为是重要的肿瘤生物标志物。然而,导致癌症发病机制的确切mtDNA突变仍不清楚。本研究的目的是调查塞内加尔患者口腔癌中线粒体DNA(mtDNA)的MT-CYB和D-Loop区域的体细胞突变。方法:通过PCR和测序评估来自45个口腔癌组织和21个对照血样的mtDNA的MT-CYB和D-Loop。将癌组织中MT-CYB和D-Loop的序列与对照序列进行比较,序列差异被识别为体细胞突变。结果:总体而言,共鉴定出389个体细胞mtDNA突变,其中大部分(79.43%)位于D-Loop区域。大多数碱基替换突变是G到A(63.93%)和T到C(16.39%)的转换。在蛋白质编码的MT-CYB基因中,观察到29个错义突变。MT-CYB的致病突变负荷为3.11%。25%的患者携带致病突变。pArg76Pro(rCRS中的pArg282Pro)是新发现的,是观察到的最常见的致病突变。结论:这些结果有力地表明mtDNA突变是口腔癌的潜在标志物。