title: High frequency of skewed X inactivation in young breast cancer patients.
abstract: BACKGROUND
  Patients with invasive ovarian cancer were recently shown to have a higher frequency of skewed X chromosome inactivation in peripheral blood cells compared to patients with borderline cancer and controls. In this study, we analysed the X inactivation pattern in peripheral blood from 216 breast cancer patients.
  
  
  METHODS
  X inactivation analysis was performed using HpaII predigestion of DNA followed by PCR of the highly polymorphic CAG repeat of the androgen receptor gene (AR), which amplifies the undigested inactive X chromosome only. The X inactivation pattern was classified as skewed when 90% or more of the cells preferentially used one X chromosome.
  
  
  RESULTS
  Young breast cancer patients (27-45 years) had a higher frequency of skewed X inactivation than young controls (13 and 1%, respectively) (p=0.009), whereas no difference was found for middle aged and older patients compared to controls of a similar age.
  
  
  CONCLUSIONS
  A germline mutation in an X linked tumour suppressor gene may give a proliferative advantage to cells with this mutation on the active X chromosome, thus causing skewed X inactivation and an increased risk for developing cancer. Another possible explanation could be that females with a constitutionally skewed X inactivation pattern are more susceptible to develop breast cancer because of an X linked low penetrance susceptibility allele that is affected by the inactivation pattern.
authors.affiliation: Institute of Medical Genetics, University of Oslo, Oslo, Norway.
authors.forename: M
authors.initials: M
authors.lastname: Kristiansen
authors.forename: A
authors.initials: A
authors.lastname: Langerød
authors.forename: G P
authors.initials: GP
authors.lastname: Knudsen
authors.forename: B L
authors.initials: BL
authors.lastname: Weber
authors.forename: A L
authors.initials: AL
authors.lastname: Børresen-Dale
authors.forename: K H
authors.initials: KH
authors.lastname: Orstavik
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D008875:Middle Aged; D018911:Trinucleotide Repeats / Q000235:genetics; D014960:X Chromosome / Q000235:genetics*