Detailed gene copy number and RNA expression analysis of the 17q12-23 region in primary breast cancers.
Chromosome region 17q12-23 commonly shows an increase in DNA copy number in breast cancers, suggesting that several oncogenes are located at this site. We performed a high-resolution expression array and comparative genomic hybridization analysis of genes mapped to the entire 17q12-23 region, to identify novel candidate oncogenes. We identified 24 genes that showed significant overexpression in breast cancers with gain of 17q12-23, compared to cancers without gain. These genes included previously identified oncogenes, together with several novel candidate oncogenes. FISH analysis using specific gene probes hybridized to tissue arrays confirmed the underlying amplification of overexpressed genes. This high-resolution analysis of the 17q12-23 region indicates that several established and novel candidate oncogenes, including a Wnt-signaling pathway member, are amplified and overexpressed within individual primary breast cancer samples. We were also able to confirm the presence of two apparently separate and reciprocally amplified groups of genes within this region. Investigation of these genes and their functional interactions will facilitate our understanding of breast oncogenesis and optimal management of this disease.
Willis
Simon
S
Molecular Pathology Laboratory, Victorian Breast Cancer Research Consortium, University of Melbourne and Peter MacCallum Cancer Institute, Melbourne, Australia.
Hutchins
Anne-Marie
AM
Hammet
Fleur
F
Ciciulla
John
J
Soo
Wee-Kheng
WK
White
David
D
van der Spek
Peter
P
Henderson
Michael A
MA
Gish
Kurt
K
Venter
Deon J
DJ
Armes
Jane E
JE
D001943:Breast Neoplasms / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005784:Gene Amplification / Q000235:genetics; D018628:Gene Dosage; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D009857:Oncogenes / Q000235:genetics; D016612:Paraffin Embedding; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D012334:RNA, Neoplasm