High incidence of somatic mitochondrial DNA mutations in human ovarian carcinomas

• Published in: Cancer research (Chicago, Ill.) Vol. 61; no. 16; pp. 5998 - 6001
• Main Authors: LIU, Vincent W. S, HONG HUI SHI, CHEUNG, Annie N. Y, PUI MAN CHIU, TSIN WAH LEUNG, NAGLEY, Phillip, LING CHUI WONG, NGAN, Hextan Y. S
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-08-2001
• Subjects: Biological and medical sciences; cytochrome b; DNA, Mitochondrial - blood; DNA, Mitochondrial - genetics; DNA, Neoplasm - blood; DNA, Neoplasm - genetics; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Mutation; Ovarian Neoplasms - genetics; Polymorphism, Genetic; RNA, Ribosomal, 16S - genetics; rRNA 12S; rRNA 16S; Tumors; Human; Carcinoma; Nucleotide sequence; Pathogenesis; Tumoral tissue; Non coding sequence; Mitochondrial DNA; Malignant tumor; Gene expression; Carcinogenesis; In vitro; Female genital diseases; Somatic mutation; Ovarian diseases; Ovary
• ISSN: 0008-5472; 1538-7445

To investigate the potential role of somatic mitochondrial DNA (mtDNA) mutations in tumorigenesis, the occurrence of mutations in mtDNA of ovarian carcinomas was studied. We sequenced the D-loop region of mtDNA of 15 primary ovarian carcinomas and their matched normal controls. Somatic mtDNA mutations were detected in 20% (3 of 15) tumor samples carrying single or multiple changes. Complete sequence analysis of the mtDNA genomes of another 10 pairs 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 represented 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 cytochrome b gene, may represent the zone of preferred mtDNA mutation in ovarian cancer. The high incidence of mtDNA mutations found in ovarian carcinomas and other human cancers suggests that genetic instability of mtDNA might play a significant role in tumorigenesis.