title: Mitochondrial D310 mutations in the early development of breast cancer.
abstract: BACKGROUND
  The role of mitochondrial DNA (mtDNA) mutations in the development of breast cancer is largely unknown. In this study, we investigated the frequency and pattern of mutations in the D310 region, the most commonly mutated region in mtDNA, in a series of breast lesions.
  
  
  METHODS
  Using capillary electrophoresis, we genotyped the D310 sequence of neoplastic epithelial cells from 23 patients with synchronous ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), 26 patients with IDC only and 29 patients with DCIS only.
  
  
  RESULTS
  A majority of DCIS (68.4%) and IDC (71.4%) lesions harbour different D310 sequences compared with their matched normal control. Specific D310 sequences were more frequently identified in tumour samples (77.1% of DCIS and 75.5% of IDC) compared with normal tissues (35.3% of normal; P<0.0001). No difference was identified between DCIS lesions with synchronous IDC and those from pure DCIS cases. In five cases, histologically normal tissue adjacent to tumour was found to share D310 sequences with the tumour, while normal tissue taken further away did not.
  
  
  CONCLUSIONS
  Although D310 alterations do not seem to be related to DCIS progression, they were found in histologically normal cells adjacent to tumour. This suggests a field of genetically altered cells, thus D310 mutations could represent a potential marker for the clonal expansion of premalignant breast cancer cells.
authors.affiliation: Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Xu
authors.forename: D
authors.initials: D
authors.lastname: Tran-Thanh
authors.forename: C
authors.initials: C
authors.lastname: Ma
authors.forename: K
authors.initials: K
authors.lastname: May
authors.forename: J
authors.initials: J
authors.lastname: Jung
authors.forename: J
authors.initials: J
authors.lastname: Vecchiarelli
authors.forename: S J
authors.initials: SJ
authors.lastname: Done
mesh_terms: D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D009154:Mutation / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial