The mitochondrial C16069T polymorphism, not mitochondrial D310 (D-loop) mononucleotide sequence variations, is associated with bladder cancer

Nasser Shakhssalim,Maryam Mobaraki,Behnam Kamalidehghan,Reza Sarhangnejad,Abolfazl Faraji,Sepideh Dadgar,Massoud Houshmand,Rozita Rosli,Mohammad Hossein Sanati

doi:10.1186/1475-2867-13-120

Abstract

BackgroundBladder cancer is a relatively common and potentially life-threatening neoplasm that ranks ninth in terms of worldwide cancer incidence. The aim of this study was to determine deletions and sequence variations in the mitochondrial displacement loop (D-loop) region from the blood specimens and tumoral tissues of patients with bladder cancer, compared to adjacent non-tumoral tissues.MethodsThe DNA from blood, tumoral tissues and adjacent non-tumoral tissues of twenty-six patients with bladder cancer and DNA from blood of 504 healthy controls from different ethnicities were investigated to determine sequence variation in the mitochondrial D-loop region using multiplex polymerase chain reaction (PCR), DNA sequencing and southern blotting analysis.ResultsFrom a total of 110 variations, 48 were reported as new mutations. No deletions were detected in tumoral tissues, adjacent non-tumoral tissues and blood samples from patients. Although the polymorphisms at loci 16189, 16261 and 16311 were not significantly correlated with bladder cancer, the C16069T variation was significantly present in patient samples compared to control samples (p < 0.05). Interestingly, there was no significant difference (p > 0.05) of C variations, including C7TC6, C8TC6, C9TC6 and C10TC6, in D310 mitochondrial DNA between patients and control samples.ConclusionOur study suggests that 16069 mitochondrial DNA D-Loop mutations may play a significant role in the etiology of bladder cancer and facilitate the definition of carcinogenesis-related mutations in human cancer.

Highlights

Human mitochondrial DNA is a 16569-bp closed circular, double-stranded molecule approximately copies per cell. mtDNA contains 37 genes, including 13 subunits involved in the electron transport chain, tRNAs, the 12S and 16S rRNAs, and a non-coding region (D-loop) located at nucleotide position 16024–(MITOMAP, 2011) [1]
Our study suggests that 16069 mitochondrial DNA Displacement loop (D-Loop) mutations may play a significant role in the etiology of bladder cancer and facilitate the definition of carcinogenesis-related mutations in human cancer
We examined the presence of mutations in the mitochondrial D-Loop sequences of tumoral tissues as compared with adjacent non-tumoral tissues from Iranian patients with bladder cancer

Summary

Introduction

Human mitochondrial DNA (mtDNA) is a 16569-bp closed circular, double-stranded molecule approximately copies per cell. mtDNA contains 37 genes, including 13 subunits involved in the electron transport chain, tRNAs, the 12S and 16S rRNAs, and a non-coding region (D-loop) located at nucleotide position 16024–(MITOMAP, 2011) [1]. MtDNA contains 37 genes, including 13 subunits involved in the electron transport chain, tRNAs, the 12S and 16S rRNAs, and a non-coding region (D-loop) located at nucleotide position 16024–. Full list of author information is available at the end of the article mutations in this region might lead to copy number and/or change in mtDNA gene expression [2]. Bladder cancer is the ninth most common cancer worldwide [3]. In Iran, bladder cancer accounts for 7.04% of all cancers [6]. Bladder cancer is a relatively common and potentially life-threatening neoplasm that ranks ninth in terms of worldwide cancer incidence. The aim of this study was to determine deletions and sequence variations in the mitochondrial displacement loop (D-loop) region from the blood specimens and tumoral tissues of patients with bladder cancer, compared to adjacent non-tumoral tissues

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Conclusion