High incidence of somatic mitochondrial DNA mutations in human ovarian carcinomas

To investigate the potential role of somatic mitochondrial DNA (mtDNA) muta tions in tumorigenesis, the occurrence of mutations in mtDNA of ovarian car cinomas was studied. We sequenced the D-loop region of mtDNA of 15 primary ovarian carcinomas and their matched normal controls. Somatic mtDNA mutatio ns were detected in 20% (3 of 15) tumor samples carrying single or multiple changes. Complete sequence analysis of the mtDNA genomes of another 10 pai rs of primary ovarian carcinomas and control tissues revealed somatic mtDNA mutations in 60% (6 of 10) of tumor samples. Most of these mutations were homoplasmic, and most were T -->C or G -->A transitions, but one represente d a differential length within a run of identical C residues. A, region of mtDNA sequence including the 16S and 12S rRNA genes, the D-loop and the cyt ochrome b gene, may represent the zone of preferred mtDNA mutation in ovari an cancer. The high incidence of mtDNA imitations found in ovarian carcinom as and other human cancers suggests that genetic instability of mtDNA might play a significant role in tumorigenesis.