BRCA1 allele-specific expression in genetic predisposed breast/ovarian cancer

Fam Cancer. 2017 Apr;16(2):167-171. doi: 10.1007/s10689-016-9940-2.


Germline allele specific expression (ASE), resulting in a lowered expression of one of the BRCA1 alleles, has been described as a possible predisposition marker in Hereditary Breast or Ovarian Cancer (HBOC), usable for molecular diagnosis in HBOC. The main objective of this prospective case-control study was to compare the proportion of ASE between controls without familial history of breast or ovarian cancer, and HBOC cases without BRCA1 or BRCA2 deleterious mutation. BRCA1 ASE evaluated on three SNPs among controls and HBOC patients without deleterious mutation were assessed by pyrosequencing. The allelic ratios and the proportion of ASE were compared between controls and cases using a Student's t test and a Fisher exact test, respectively. The linearity and reproducibility of the ASE dosage was demonstrated with R2 > 0.99 and a coefficient of variation below 10 %, and ASE was detected in two positive controls harbouring BRCA1 truncated mutations. In the heterozygote population, composed of 99/264 controls (37.5 %) and 96/227 patients (42.3 %), we detected a 5 % ASE without truncated mutations, in each population. We failed to detect any significant difference of ASE between controls and patients. So far, BRCA1 Allelic specific expression is not usable in routine diagnosis as a possible predisposition marker in HBOC patients except for the detection of truncated mutations.

Keywords: Allele specific expression; BRCA1; Breast; Cancer; Ovarian.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Allelic Imbalance / genetics*
  • BRCA1 Protein / genetics*
  • Biomarkers, Tumor / genetics
  • Case-Control Studies
  • Female
  • Genes, BRCA1*
  • Genetic Predisposition to Disease / genetics*
  • Germ-Line Mutation / genetics*
  • Hereditary Breast and Ovarian Cancer Syndrome / genetics*
  • Heterozygote
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Young Adult


  • BRCA1 Protein
  • BRCA1 protein, human
  • Biomarkers, Tumor