title: Sequencing, transcript identification, and quantitative gene expression profiling in the breast cancer loss of heterozygosity region 16q24.3 reveal three potential tumor-suppressor genes.
abstract: Loss of heterozygosity (LOH) of chromosome 16q24.3 is a common genetic alteration observed in invasive ductal and lobular breast carcinomas. We constructed a physical map and generated genomic DNA sequence data spanning 2.4 Mb in this region. Detailed in silico and in vitro analyses of the genomic sequence data enabled the identification of 104 genes. It was hypothesized that tumor-suppressor genes would exhibit marked mRNA expression variability in a panel of breast cancer cell lines as a result of downregulation due to mutation or hypermethylation. We examined the mRNA expression profiles of the genes identified at 16q24.3 in normal breast, a normal breast epithelial cell line, and several breast cancer cell lines exhibiting 16q24.3 LOH. Three of the genes, CYBA, Hs.7970, and CBFA2T3, exhibited variability ten times higher than the baseline. The possible role of these genes as tumor suppressors is discussed.
authors.affiliation: Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, South Australia, 5006, Australia.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Powell
authors.forename: Alison E
authors.initials: AE
authors.lastname: Gardner
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Bais
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Hinze
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Baker
authors.forename: Scott
authors.initials: S
authors.lastname: Whitmore
authors.forename: Joanna
authors.initials: J
authors.lastname: Crawford
authors.forename: Marina
authors.initials: M
authors.lastname: Kochetkova
authors.forename: Hayley E
authors.initials: HE
authors.lastname: Spendlove
authors.forename: Norman A
authors.initials: NA
authors.lastname: Doggett
authors.forename: Grant R
authors.initials: GR
authors.lastname: Sutherland
authors.forename: David F
authors.initials: DF
authors.lastname: Callen
authors.forename: Gabriel
authors.initials: G
authors.lastname: Kremmidiotis
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16; D005260:Female; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D006801:Humans; D019656:Loss of Heterozygosity; D020161:Physical Chromosome Mapping; D017422:Sequence Analysis, DNA