Somatic mitochondrial DNA mutations in primary and metastatic ovarian cancer

• Published in: Gynecologic oncology Vol. 104; no. 1; pp. 129 - 133
• Main Authors: Van Trappen, P.O, Cullup, T, Troke, R, Swann, D, Shepherd, J.H, Jacobs, I.J, Gayther, S.A, Mein, C.A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2007
• Subjects: Base Sequence; D-loop; DNA, Mitochondrial - genetics; DNA, Neoplasm - genetics; Female; Hematology, Oncology and Palliative Medicine; Humans; Mitochondrial DNA; Mutation; Mutations; Obstetrics and Gynecology; Ovarian cancer; Ovarian Neoplasms - genetics; Polymorphism, Genetic; Polymorphisms; Mutations; Mitochondrial DNA; D-loop; Polymorphisms; Ovarian cancer
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2006.07.010

Abstract Objective To date, most mtDNA mutations in cancer have been identified in the control region (D-loop) containing the major promoters. However, almost all studies used one sample per tumor and there is no clear evidence whether metastatic deposits harbor different mtDNA variants. To establish whether different mtDNA variants can be found in the same cancer but at different sites, we analyzed a series of unilateral and bilateral primary epithelial ovarian cancers as well as paired metastatic tumor deposits. Methods We sequenced the D-loop region in 52 different tumor samples of 35 ovarian cancer cases, as well as matched normal tissues. Seventeen of those 35 cases had bilateral ovarian cancer, with a sample from each tumor analyzed. Results Eighty-six polymorphisms (4 new in ovarian cancer) were detected, and 9 different somatic mtDNA mutations were found in 26% (9 of 35) of ovarian cancer cases; all were homoplasmic in nature. Six of the mutations were novel in ovarian cancer. In 24% (4 of 17) of cases with bilateral ovarian tumors, different mtDNA variants were found between paired tumors, suggesting the presence of different clonal populations of cancer cells. Metastatic tumor deposits showed identical mtDNA variants to those found in at least one of the ovarian tumors in cases with bilateral ovarian cancer. Conclusion Our data demonstrate that multiple tumor samples from the same patient may harbor different mtDNA variants.