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Mitochondrion. 2014 May;16:73-82. doi: 10.1016/j.mito.2013.07.001. Epub 2013 Jul 10.

Mitochondrial DNA variation analysis in cervical cancer.

Author information

1
Division of Biotechnology, Manipal Life Sciences Centre, Manipal University, Manipal, Karnataka, India.
2
Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal University, Manipal, Karnataka, India.
3
Centre for Cellular and Molecular Biology, Hyderabad, India.
4
Division of Biotechnology, Manipal Life Sciences Centre, Manipal University, Manipal, Karnataka, India. Electronic address: ksatyamoorthy@manipal.edu.

Abstract

This study was undertaken to investigate the mitochondrial DNA (mtDNA) variation in non-malignant and malignant cervical tissue samples. We have identified 229 and 739 variations non-malignant and malignant tissues respectively distributed over 321 locations in the D-loop (50 in non-malignant and 166 in malignant; 216 variations), coding region (139 in non-malignant and 455 in malignant; 594 variations) tRNA and rRNA genes (39 in non-malignant and 119 in malignant; 158 variations). Besides, 77 novel and 34 various other disease associated variations were identified in non-malignant and malignant samples. A total of 236 tumor specific variations in 201 locations representing 30.1% in D-loop, 59.3% in coding regions and 10.6% in RNA genes were also identified. Our study shows that D loop (in 67 locations) is highly altered followed by ND5 (35 locations) region. Moreover, mtDNA alterations were significantly higher in malignant samples by two tailed Fisher's exact test (P≤0.05) with decreased mtDNA copy numbers. Bioinformatic analysis of 59 non-synonymous changes predicted several variations as damaging leading to decreased stability of the proteins. Taken together, mtDNA is highly altered in cervical cancer and functional studies are needed to be investigated to understand the consequence of these variations in cervical carcinogenesis and their potential application as biomarkers.

KEYWORDS:

Cervical cancer; Copy number; D loop and coding region; HPV; Haplogroup; mtDNA

PMID:
23851045
DOI:
10.1016/j.mito.2013.07.001
[Indexed for MEDLINE]
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