Prediction of BRCA2-association in hereditary breast carcinomas using array-CGH

Breast Cancer Res Treat. 2012 Apr;132(2):379-89. doi: 10.1007/s10549-010-1016-7. Epub 2010 Jul 8.


Germline mutations in BRCA1/2 increase the lifetime risk for breast and ovarian cancer dramatically. Identification of such mutations is important for optimal treatment decisions and pre-symptomatic mutation screening in family members. Although current DNA diagnostics is able to identify many different mutations, it remains unclear, how many BRCA2-associated breast cancer cases remain unidentified as such. In addition, mutation scanning detects many unclassified variants (UV) for which the clinical relevance is uncertain. Therefore, our aim was to develop a test to identify BRCA2-association in breast tumors based on the genomic signature. A BRCA2-classifier was built using array-CGH profiles of 28 BRCA2-mutated and 28 sporadic breast tumors. The classifier was validated on an independent group of 19 BRCA2-mutated and 19 sporadic breast tumors. Subsequently, we tested 89 breast tumors from suspected hereditary breast (and ovarian) cancer (HBOC) families, in which either no BRCA1/2 mutation or an UV had been found by routine diagnostics. The classifier showed a sensitivity of 89% and specificity of 84% on the validation set of known BRCA2-mutation carriers and sporadic tumor cases. Of the 89 HBOC cases, 17 presented a BRCA2-like profile. In three of these cases additional indications for BRCA2-deficiency were found. Chromosomal aberrations that were specific for BRCA2-mutated tumors included loss on chromosome arm 13q and 14q, and gain on 17q. Since we could separate BRCA1-like, BRCA2-like, and sporadic-like tumors, using our current BRCA2- and previous BRCA1-classifier, this method of breast tumor classification could be applied as additional test for current diagnostics to help clinicians in decision making and classifying sequence variants of unknown significance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics*
  • Biomarkers, Tumor / analysis
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / classification
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / chemistry
  • Carcinoma, Ductal, Breast / classification
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / pathology
  • Chromosome Aberrations
  • Comparative Genomic Hybridization*
  • DNA Copy Number Variations
  • DNA Methylation
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease
  • Genetic Testing / methods*
  • Heredity
  • Humans
  • Immunohistochemistry
  • Loss of Heterozygosity
  • Middle Aged
  • Mutation*
  • Neoplasm Invasiveness
  • Netherlands
  • Oligonucleotide Array Sequence Analysis*
  • Phenotype
  • Predictive Value of Tests
  • Promoter Regions, Genetic
  • Receptors, Estrogen / analysis
  • Reproducibility of Results
  • Sensitivity and Specificity


  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Biomarkers, Tumor
  • Receptors, Estrogen