title: Prediction of BRCA1-association in hereditary non-BRCA1/2 breast carcinomas with array-CGH.
abstract: BACKGROUND
  While new defects in BRCA1 are still being found, it is unclear whether current breast cancer diagnostics misses many BRCA1-associated cases. A reliable test that is able to indicate the involvement of BRCA1 deficiency in cancer genesis could support decision making in genetic counselling and clinical management. To find BRCA1-specific markers and explore the effectiveness of the current diagnostic strategy, we designed a classification method, validated it and examined whether we could find BRCA1-like breast tumours in a group of patients initially diagnosed as non-BRCA1/2 mutation carriers.
  
  
  METHODS
  A classifier was built based on array-CGH profiles of 18 BRCA1-related and 32 control breast tumours, and validated on independent sets of 16 BRCA1-related and 16 control breast carcinomas. Subsequently, we applied the classifier to 48 breast tumours of patients from Hereditary Breast and Ovarian Cancer (HBOC) families in whom no germ line BRCA1/BRCA2 mutations were identified.
  
  
  RESULTS
  The classifier showed an accuracy of 91% when applied to the validation sets. In 48 non-BRCA1/2 patients, only two breast tumours presented a BRCA1-like CGH profile. Additional evidence for BRCA1 dysfunction was found in one of these tumours.
  
  
  CONCLUSIONS
  We here describe the specific chromosomal aberrations in BRCA1-related breast carcinomas. We developed a predictive genetic test for BRCA1-association and show that BRCA1-related tumours can still be identified in HBOC families after routine DNA diagnostics.
authors.affiliation: Division of Experimental Therapy, The Netherlands Cancer Institute NKI/AvL, 1066CX, Amsterdam, The Netherlands. s.joosse@nki.nl
authors.forename: Simon A
authors.initials: SA
authors.lastname: Joosse
authors.forename: Erik H
authors.initials: EH
authors.lastname: van Beers
authors.forename: Ivon H G
authors.initials: IH
authors.lastname: Tielen
authors.forename: Hugo
authors.initials: H
authors.lastname: Horlings
authors.forename: Johannes L
authors.initials: JL
authors.lastname: Peterse
authors.forename: Nicoline
authors.initials: N
authors.lastname: Hoogerbrugge
authors.forename: Marjolijn J
authors.initials: MJ
authors.lastname: Ligtenberg
authors.forename: Lodewyk F A
authors.initials: LF
authors.lastname: Wessels
authors.forename: Priscilla
authors.initials: P
authors.lastname: Axwijk
authors.forename: Senno
authors.initials: S
authors.lastname: Verhoef
authors.forename: Frans B L
authors.initials: FB
authors.lastname: Hogervorst
authors.forename: Petra M
authors.initials: PM
authors.lastname: Nederlof
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D019656:Loss of Heterozygosity; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests
chemical_list: D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm