title: Platform comparisons for identification of breast cancers with a BRCA-like copy number profile.
abstract: Previously, we employed bacterial artificial chromosome (BAC) array comparative genomic hybridization (aCGH) profiles from BRCA1 and -2 mutation carriers and sporadic tumours to construct classifiers that identify tumour samples most likely to harbour BRCA1 and -2 mutations, designated 'BRCA1 and -2-like' tumours, respectively. The classifiers are used in clinical genetics to evaluate unclassified variants, and patients for which no good quality germline DNA is available. Furthermore, we have shown that breast cancer patients with BRCA-like tumour aCGH profiles benefit substantially from platinum-based chemotherapy, potentially due to their inability to repair DNA double strand breaks (DSB), providing a further important clinical application for the classifiers. The BAC array technology has been replaced with oligonucleotide arrays. To continue clinical use of existing classifiers, we mapped oligonucleotide aCGH data to the BAC domain, such that the oligonucleotide profiles can be employed as in the BAC classifier. We demonstrate that segmented profiles derived from oligonucleotide aCGH show high correlation with BAC aCGH profiles. Furthermore, we trained a support vector machine score to objectify aCGH profile quality. Using the mapped oligonucleotide aCGH data, we show equivalence in classification of biologically relevant cases between BAC and oligonucleotide data. Furthermore, the predicted benefit of DSB inducing chemotherapy due to a homologous recombination defect is retained. We conclude that oligonucleotide aCGH data can be mapped to and used in the previously developed and validated BAC aCGH classifiers. Our findings suggest that it is possible to map copy number data from any other technology in a similar way.
authors.affiliation: Division of Molecular Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Schouten
authors.forename: Ewald
authors.initials: E
authors.lastname: van Dyk
authors.forename: Linde M
authors.initials: LM
authors.lastname: Braaf
authors.forename: Lennart
authors.initials: L
authors.lastname: Mulder
authors.forename: Esther H
authors.initials: EH
authors.lastname: Lips
authors.forename: Jorma J
authors.initials: JJ
authors.lastname: de Ronde
authors.forename: Laura
authors.initials: L
authors.lastname: Holtman
authors.forename: Jelle
authors.initials: J
authors.lastname: Wesseling
authors.forename: Michael
authors.initials: M
authors.lastname: Hauptmann
authors.forename: Lodewyk F A
authors.initials: LF
authors.lastname: Wessels
authors.forename: Sabine C
authors.initials: SC
authors.lastname: Linn
authors.forename: Petra M
authors.initials: PM
authors.lastname: Nederlof
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D022202:Chromosomes, Artificial, Bacterial; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D008490:Medical Informatics; D009367:Neoplasm Staging; D012680:Sensitivity and Specificity
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein