title: BRCA1/2 mutation status influences somatic genetic progression in inherited and sporadic epithelial ovarian cancer cases.
abstract: Metaphase comparative genomic hybridization was used to analyze the spectrum of genetic alterations in 141 epithelial ovarian cancers from BRCA1 and BRCA2 mutation carriers, individuals with familial non-BRCA1/2 epithelial ovarian cancer, and women with nonfamilial epithelial ovarian cancer. Multiple genetic alterations were identified in almost all tumors. The high frequency with which some alterations were identified suggests the location of genes that are commonly altered during ovarian tumor development. In multiple chromosome regions, there were significant differences in alteration frequency between the four tumor types suggesting that BRCA1/2 mutation status and a family history of ovarian cancer influences the somatic genetic pathway of ovarian cancer progression. These findings were supported by hierarchical cluster analysis, which identified genetic events that tend to occur together during tumorigenesis and several alterations that were specific to tumors of a particular type. In addition, some genetic alterations were strongly associated with differences in tumor differentiation and disease stage. Taken together, these data provide molecular genetic evidence to support previous findings from histopathological studies, which suggest that clinical features of ovarian and breast tumors differ with respect to BRCA1/2 mutation status and/or cancer family history.
authors.affiliation: Department of Oncology, Strangeways Research Laboratories, Cambridge, United Kingdom.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Ramus
authors.forename: Paul D P
authors.initials: PD
authors.lastname: Pharoah
authors.forename: Patricia
authors.initials: P
authors.lastname: Harrington
authors.forename: Carole
authors.initials: C
authors.lastname: Pye
authors.forename: Bruce
authors.initials: B
authors.lastname: Werness
authors.forename: Lynda
authors.initials: L
authors.lastname: Bobrow
authors.forename: Ayse
authors.initials: A
authors.lastname: Ayhan
authors.forename: Dagan
authors.initials: D
authors.lastname: Wells
authors.forename: Ami
authors.initials: A
authors.lastname: Fishman
authors.forename: Martin
authors.initials: M
authors.lastname: Gore
authors.forename: Richard A
authors.initials: RA
authors.lastname: DiCioccio
authors.forename: M Steven
authors.initials: MS
authors.lastname: Piver
authors.forename: Alice S
authors.initials: AS
authors.lastname: Whittemore
authors.forename: Bruce A J
authors.initials: BA
authors.lastname: Ponder
authors.forename: Simon A
authors.initials: SA
authors.lastname: Gayther
mesh_terms: D002869:Chromosome Aberrations; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D009693:Nucleic Acid Hybridization; D010051:Ovarian Neoplasms / Q000235:genetics*