title: Genome-wide mitochondrial DNA sequence variations and lower expression of OXPHOS genes predict mitochondrial dysfunction in oral cancer tissue.
abstract: Several studies reported that mtDNA mutations may play important roles in carcinogenesis although the mechanism is not clear yet. Most of the studies compared mtDNA sequences in a tumor with those in normal tissues from different individuals ignoring inter-individual variations. In this study, 271 SNPs, 7 novel SNPs (or SNVs), and 15 somatic mutations were detected in mtDNA of 8 oral cancer tissues with respect to reference (rCRS) and adjacent normal tissues, respectively, using Ion PGM next generation sequencing method. Most of the sequence variations (76 SNPs and 1 somatic) are present in D-loop region followed by CyB (36 SNPs), ATP6 (24 SNPs), ND5 (17 SNPs and 5 somatic), ND4 (18 coding and 2 somatic) and other non-coding and coding DNA sequences. A total of 53 and 8 non-synonymous SNPs and somatic mutations, respectively, were detected in tumor tissues and some of these variations may have deleterious effects on the protein function as predicted by bioinformatic analysis. Moreover, significantly low mtDNA contents and expression of several mitochondrial genes in tumor compared to adjacent normal tissues may have also affected mitochondrial functions. Taken together, this study suggests that mtDNA mutations as well as low expression of mtDNA coded genes may play important roles in tumor growth. Although the sample size is low, an important aspect of the study is the use of adjacent control tissues to find out somatic mutations and a change in the expression of mitochondrial genes, to rule out inter-individual and inter-tissue variations which are important issues in the study of mitochondrial genomics.
authors.affiliation: Human Genetics Unit, Indian Statistical Institute, 203 B T Road, Kolkata, 700108, India.
authors.forename: Esita
authors.initials: E
authors.lastname: Chattopadhyay
authors.affiliation: Fred Hutchinson Cancer Research center, University of Washington, Seattle, WA, USA.
authors.forename: Navonil
authors.initials: N
authors.lastname: De Sarkar
authors.affiliation: Human Genetics Unit, Indian Statistical Institute, 203 B T Road, Kolkata, 700108, India.
authors.forename: Richa
authors.initials: R
authors.lastname: Singh
authors.affiliation: Human Genetics Unit, Indian Statistical Institute, 203 B T Road, Kolkata, 700108, India.
authors.forename: Anindita
authors.initials: A
authors.lastname: Ray
authors.affiliation: Human Genetics Unit, Indian Statistical Institute, 203 B T Road, Kolkata, 700108, India.
authors.forename: Roshni
authors.initials: R
authors.lastname: Roy
authors.affiliation: Department of Oral Pathology, Guru Nanak Institute of Dental Science & Research, 157/F Nilganj Road, Kolkata, 700114, India.
authors.forename: Ranjan Rashmi
authors.initials: RR
authors.lastname: Paul
authors.affiliation: Department of Oral Pathology, Guru Nanak Institute of Dental Science & Research, 157/F Nilganj Road, Kolkata, 700114, India.
authors.forename: Mousumi
authors.initials: M
authors.lastname: Pal
authors.affiliation: Department of Oral Pathology, Dr. R Ahmed Dental College and Hospital, 114- AJC Bose Road, Kolkata, 700014, India.
authors.forename: Sandip
authors.initials: S
authors.lastname: Ghose
authors.affiliation: Department of Bioinformatics, Maulana Abul Kalam Azad University of Technology, West Bengal (formerly known as WBUT), BF-142, Sector 1, Salt Lake City, Kolkata, 700064, India.
authors.forename: Subhrendu
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Bioinformatics, Maulana Abul Kalam Azad University of Technology, West Bengal (formerly known as WBUT), BF-142, Sector 1, Salt Lake City, Kolkata, 700064, India.
authors.forename: Debajyoti
authors.initials: D
authors.lastname: Kabiraj
authors.affiliation: Department of Bioinformatics, Maulana Abul Kalam Azad University of Technology, West Bengal (formerly known as WBUT), BF-142, Sector 1, Salt Lake City, Kolkata, 700064, India.|Department of Biotechnology, Maulana Abul Kalam Azad University of Technology West Bengal (formerly known as WBUT), BF-142, Sector 1, Salt Lake City, Kolkata, 700064, India.
authors.forename: Raja
authors.initials: R
authors.lastname: Banerjee
authors.affiliation: Human Genetics Unit, Indian Statistical Institute, 203 B T Road, Kolkata, 700108, India. broy@isical.ac.in.
authors.forename: Bidyut
authors.initials: B
authors.lastname: Roy
mesh_terms: D000328:Adult; D000368:Aged; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D050259:Genes, Mitochondrial / Q000235:genetics; D014644:Genetic Variation; D054629:Genome, Mitochondrial / Q000235:genetics*; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D020641:Polymorphism, Single Nucleotide
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins
keywords: Expression; Mutation; Next generation sequencing; Oral cancer tissue; mtDNA