title: Somatic mitochondrial DNA mutations in primary and metastatic ovarian cancer.
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.
  
  
  CONCLUSIONS
  Our data demonstrate that multiple tumor samples from the same patient may harbor different mtDNA variants.
authors.affiliation: Gynaecological Cancer Centre and Centre for Translational Oncology, Institute of Cancer and CR-UK Clinical Centre, Barts and The London, Queen Mary's School of Medicine and Dentistry, John Vane Science Centre, London, UK. pvta@sgyn.azm.nl
authors.forename: P O
authors.initials: PO
authors.lastname: Van Trappen
authors.forename: T
authors.initials: T
authors.lastname: Cullup
authors.forename: R
authors.initials: R
authors.lastname: Troke
authors.forename: D
authors.initials: D
authors.lastname: Swann
authors.forename: J H
authors.initials: JH
authors.lastname: Shepherd
authors.forename: I J
authors.initials: IJ
authors.lastname: Jacobs
authors.forename: S A
authors.initials: SA
authors.lastname: Gayther
authors.forename: C A
authors.initials: CA
authors.lastname: Mein
mesh_terms: D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm