Multiple genes at 17q23 undergo amplification and overexpression in breast cancer.
Studies by comparative genomic hybridization imply that amplification of the chromosomal region 17q22-q24 is common in breast cancer. Here, amplification and expression levels of six known genes located at 17q23 were examined in breast cancer cell lines. Four of them (RAD51C, S6K, PAT1, and TBX2) were found to be highly amplified and overexpressed. To investigate the involvement of these genes in vivo, fluorescence in situ hybridization analysis of a tissue microarray containing 372 primary breast cancers was used. S6K, PAT1, and TBX2 were coamplified in about 10% of tumors, whereas RADS1C amplification was seen in only 3% of tumors. Expression analysis in 12 primary tumors showed that RAD51C and S6K were consistently expressed in all cases in which they were amplified and also in some tumors without amplification. These data suggest that 17q23 amplification results in simultaneous up-regulation of several genes, whose increased biological activity may jointly contribute to the more aggressive clinical course observed in patients with 17q23-amplified tumors.
Bärlund
M
M
Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere, Finland.
Monni
O
O
Kononen
J
J
Cornelison
R
R
Torhorst
J
J
Sauter
G
G
Kallioniemi OLLI-P
Kallioniemi
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D009857:Oncogenes / Q000235:genetics; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins; D051135:Rad51 Recombinase; D019893:Ribosomal Protein S6 Kinases / Q000096:biosynthesis / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000235:genetics
D004268:DNA-Binding Proteins; D015513:Oncogene Proteins; C103266:PAT1 protein, S cerevisiae; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; D019893:Ribosomal Protein S6 Kinases; C495153:RAD51 protein, human; D051135:Rad51 Recombinase