Research article

Limited clinical relevance of mitochondrial DNA mutation and gene expression analyses in ovarian cancer

Piotr Bragoszewski¹ , Jolanta Kupryjanczyk² , Ewa Bartnik^3,4 , Andrea Rachinger⁵ and Jerzy Ostrowski¹

¹  Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, Warsaw, Poland

²  Department of Molecular Pathology, the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, Warsaw, Poland

³  Institute of Genetics and Biotechnology, University of Warsaw, Warsaw, Poland

⁴  Institute of Biochemistry and Biophysics, Pawinskiego 5, Warsaw, Poland

⁵  Marie-Curie Scholarship, Institute of Biochemistry and Biophysics, Pawinskiego 5, Warsaw, Poland

author email corresponding author email

BMC Cancer 2008, 8:292doi:10.1186/1471-2407-8-292

Published:	8 October 2008

Abstract

Background

In recent years, numerous studies have investigated somatic mutations in mitochondrial DNA in various tumours. The observed high mutation rates might reflect mitochondrial deregulation; consequently, mutation analyses could be clinically relevant. The purpose of this study was to determine if mutations in the mitochondrial D-loop region and/or the level of mitochondrial gene expression could influence the clinical course of human ovarian carcinomas.

Methods

We sequenced a 1320-base-pair DNA fragment of the mitochondrial genome (position 16,000-750) in 54 cancer samples and in 44 corresponding germline control samples. In addition, six transcripts (MT-ATP6, MT-CO1, MT-CYB, MT-ND1, MT-ND6, and MT-RNR1) were quantified in 62 cancer tissues by real-time RT-PCR.

Results

Somatic mutations in the D-loop sequence were found in 57% of ovarian cancers. Univariate analysis showed no association between mitochondrial DNA mutation status or mitochondrial gene expression and any of the examined clinicopathologic parameters. A multivariate logistic regression model revealed that the expression of the mitochondrial gene RNR1 might be used as a predictor of tumour sensitivity to chemotherapy.

Conclusion

In contrast to many previously published papers, our study indicates rather limited clinical relevance of mitochondrial molecular analyses in ovarian carcinomas. These discrepancies in the clinical utility of mitochondrial molecular tests in ovarian cancer require additional large, well-designed validation studies.