title: Candidate tumor-suppressor genes on chromosome arm 8p in early-onset and high-grade breast cancers.
abstract: Loss of genetic material from chromosome arm 8p occurs commonly in breast carcinomas, suggesting that this region is the site of one or more tumor-suppressor genes (TSGs). Comparative genomic hybridization analysis showed that 8p loss is more common in breast cancers from pre-menopausal compared with post-menopausal patients, as well as in high-grade breast cancers, regardless of the menopausal status. Subsequent high-resolution gene expression profiling of genes mapped to chromosome arm 8p, on an extended cohort of clinical tumor samples, indicated a similar dichotomy of breast cancer clinicopathologic types. Some of these genes showed differential downregulation in early-onset and later-onset, high-grade cancers compared with lower-grade, later-onset cancers. Three such genes were analysed further by in situ technologies, performed on tissue microarrays representing breast tumor and normal tissue samples. PCM1, which encodes a centrosomal protein, and DUSP4/MKP-2, which encodes a MAP kinase phosphatase, both showed frequent gene and protein loss in carcinomas. In contrast, there was an excess of cases showing loss of expression in the absence of reduced gene copy number of SFRP1, which encodes a dominant-negative receptor for Wnt-family ligands. These candidate TSGs may constitute some of the molecular drivers of chromosome arm 8p loss in breast carcinogenesis.
authors.affiliation: Molecular Pathology Laboratory, Victorian Breast Cancer Research Consortium, Australia. jane.armes@svhm.org.au
authors.forename: Jane E
authors.initials: JE
authors.lastname: Armes
authors.forename: Fleur
authors.initials: F
authors.lastname: Hammet
authors.forename: Melanie
authors.initials: M
authors.lastname: de Silva
authors.forename: John
authors.initials: J
authors.lastname: Ciciulla
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Ramus
authors.forename: Wee-Kheng
authors.initials: WK
authors.lastname: Soo
authors.forename: Alexis
authors.initials: A
authors.lastname: Mahoney
authors.forename: Natalia
authors.initials: N
authors.lastname: Yarovaya
authors.forename: Michael A
authors.initials: MA
authors.lastname: Henderson
authors.forename: Kurt
authors.initials: K
authors.lastname: Gish
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Hutchins
authors.forename: Gareth R
authors.initials: GR
authors.lastname: Price
authors.forename: Deon J
authors.initials: DJ
authors.lastname: Venter
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D002872:Chromosome Deletion; D002898:Chromosomes, Human, Pair 8; D005260:Female; D018628:Gene Dosage; D016147:Genes, Tumor Suppressor; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008593:Menopause