title: D-loop somatic mutations and ∼5 kb "common" deletion in mitochondrial DNA: important molecular markers to distinguish oral precancer and cancer.
abstract: 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.
authors.affiliation: Human Genetics Unit, Indian Statistical Institute, 203 B.T. Road, Kolkata, 700108, India.
authors.forename: Sayantan
authors.initials: S
authors.lastname: Datta
authors.forename: Esita
authors.initials: E
authors.lastname: Chattopadhyay
authors.forename: Jay Gopal
authors.initials: JG
authors.lastname: Ray
authors.forename: Mousumi
authors.initials: M
authors.lastname: Majumder
authors.forename: Puspita Das
authors.initials: PD
authors.lastname: Roy
authors.forename: Bidyut
authors.initials: B
authors.lastname: Roy
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D004272:DNA, Mitochondrial / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007972:Leukoplakia, Oral / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D017382:Reactive Oxygen Species / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm; D017382:Reactive Oxygen Species