title: Comparative genomic hybridization profiles in human BRCA1 and BRCA2 breast tumors highlight differential sets of genomic aberrations.
abstract: BRCA1 or BRCA2 germline mutations cause approximately 30% of breast cancers within high-risk families. This represents 5% of total breast cancer incidence. Although BRCA1 and BRCA2 are both implicated in DNA repair and genome stability, it is unknown whether BRCA1 and BRCA2 are associated with similar or distinct diseases. In a previous study we reported that BRCA1-related breast carcinomas show a distinct genomic profile as determined by comparative genomic hybridization (CGH). We now hypothesize that, if functionally equivalent, mutations in BRCA1 and BRCA2 would result in similar genomic profiles in tumors. Here we report the chromosomal gains and losses as measured by CGH in 25 BRCA2-associated breast tumors and compared them with our existing 36 BRCA1 and 30 control profiles. We compared all chromosomal regions and determined the regions of differential gain or loss between tumor classes and controls. BRCA2 and control tumors have very similar genomic profiles. As a consequence, and in contrast to BRCA1-associated tumors, CGH profiles from BRCA2-associated tumors could not be distinguished from control tumors using the classification methodology as we have developed before. The largest number of significant differences existed between BRCA1 and controls, followed by BRCA1 compared with BRCA2, suggesting different tumor development pathways for BRCA1 and BRCA2.
authors.affiliation: Department of Pathology and Familial Cancer Clinic of the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. e.v.beers@nki.nl
authors.forename: Erik H
authors.initials: EH
authors.lastname: van Beers
authors.forename: Tibor
authors.initials: T
authors.lastname: van Welsem
authors.forename: Lodewyk F A
authors.initials: LF
authors.lastname: Wessels
authors.forename: Yunlei
authors.initials: Y
authors.lastname: Li
authors.forename: Rogier A
authors.initials: RA
authors.lastname: Oldenburg
authors.forename: Peter
authors.initials: P
authors.lastname: Devilee
authors.forename: Cees J
authors.initials: CJ
authors.lastname: Cornelisse
authors.forename: Senno
authors.initials: S
authors.lastname: Verhoef
authors.forename: Frans B L
authors.initials: FB
authors.lastname: Hogervorst
authors.forename: Laura J
authors.initials: LJ
authors.lastname: van't Veer
authors.forename: Petra M
authors.initials: PM
authors.lastname: Nederlof
mesh_terms: D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics*; D002869:Chromosome Aberrations; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D015894:Genome, Human; D018095:Germ-Line Mutation; D006801:Humans; D009693:Nucleic Acid Hybridization