title: Analysis of gene alterations of mitochondrial DNA D-loop regions to determine breast cancer clonality.
abstract: BACKGROUND
  It has been a challenge to determine breast cancer clonality accurately. The aim of the present study was to assess methods using formalin-fixed paraffin-embedded (FFPE) tissue to differentiate new primary tumours from true recurrences that are associated with poorer prognoses and often require more aggressive treatment.
  
  
  METHODS
  We investigated the novel method of analysing gene alterations of mitochondrial DNA D-loop region (GAMDDL) and compared it with the conventional method of analysing the X-chromosome-linked human androgen receptor (HUMARA). The FFPE sections of primary and secondary breast cancers, the non-neoplastic mammary gland, and lymph nodes were examined.
  
  
  RESULTS
  Informative rates for HUMARA, GAMDDL, and combined analyses were 42.1%, 76.9%, and 89.5%, respectively. All of the 10 contralateral breast cancers were determined to be non-clonal. In contrast, 3 out of 8 (37.5%) of the ipsilateral secondary tumours shared a clonal origin with the primary tumour and were classified as true recurrences, whereas 4 out of 8 (50%) were classified as new primary tumours.
  
  
  CONCLUSIONS
  GAMDDL analysis represents a novel and useful molecular method for examining the precise cell lineages of primary and secondary tumours, and was more accurate than HUMARA in determining clonality.
authors.affiliation: Department of Pathology, Nihon University School of Medicine, 30-1 Ohyaguchikami-cho, Itabashi-ku, Tokyo 173-8610, Japan. masuda.shinobu@nihon-u.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Masuda
authors.forename: T
authors.initials: T
authors.lastname: Kadowaki
authors.forename: N
authors.initials: N
authors.lastname: Kumaki
authors.forename: X
authors.initials: X
authors.lastname: Tang
authors.forename: Y
authors.initials: Y
authors.lastname: Tokuda
authors.forename: S
authors.initials: S
authors.lastname: Yoshimura
authors.forename: S
authors.initials: S
authors.lastname: Takekoshi
authors.forename: R Y
authors.initials: RY
authors.lastname: Osamura
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D041321:Chromosomes, Human, X; D002999:Clone Cells / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005557:Formaldehyde; D006801:Humans; D061346:Laser Capture Microdissection; D008198:Lymph Nodes / Q000473:pathology; D042361:Mammary Glands, Human / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000175:diagnosis* / Q000235:genetics; D016612:Paraffin Embedding; D016133:Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics
chemical_list: C410798:AR protein, human; D004272:DNA, Mitochondrial; D011944:Receptors, Androgen; D005557:Formaldehyde