Sequencing, transcript identification, and quantitative gene expression profiling in the breast cancer loss of heterozygosity region 16q24.3 reveal three potential tumor-suppressor genes.
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.
Powell
Jason A
JA
Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, South Australia, 5006, Australia.
Gardner
Alison E
AE
Bais
Anthony J
AJ
Hinze
Susan J
SJ
Baker
Elizabeth
E
Whitmore
Scott
S
Crawford
Joanna
J
Kochetkova
Marina
M
Spendlove
Hayley E
HE
Doggett
Norman A
NA
Sutherland
Grant R
GR
Callen
David F
DF
Kremmidiotis
Gabriel
G
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