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


CONCLUSIONS
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.
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. pwain@poczta.onet.pl
Piotr
P
Bragoszewski
Jolanta
J
Kupryjanczyk
Ewa
E
Bartnik
Andrea
A
Rachinger
Jerzy
J
Ostrowski
D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004272:DNA, Mitochondrial / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D015870:Gene Expression; D050259:Genes, Mitochondrial; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric
D000970:Antineoplastic Agents; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins