Faculty Collaboration Database

Genome-wide mitochondrial DNA sequence variations and lower expression of OXPHOS genes predict mitochondrial dysfunction in oral cancer tissue. Tumour Biol 2016 Sep;37(9):11861-11871

Date

10/27/2016

Pubmed ID

27055661

DOI

10.1007/s13277-016-5026-x

Scopus ID

2-s2.0-84964038436 (requires institutional sign-in at Scopus site)   10 Citations

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.

Author List

Chattopadhyay E, De Sarkar N, Singh R, Ray A, Roy R, Paul RR, Pal M, Ghose S, Ghosh S, Kabiraj D, Banerjee R, Roy B

Author

Navonil De Sarkar PhD Assistant Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
DNA, Mitochondrial
Female
Gene Expression Regulation, Neoplastic
Genes, Mitochondrial
Genetic Variation
Genome, Mitochondrial
Genomics
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Mitochondria
Mitochondrial Proteins
Mouth Neoplasms
Mutation
Polymorphism, Single Nucleotide