Identification of candidate growth promoting genes in ovarian cancer through integrated copy number and expression analysis.
Ovarian cancer is a disease characterised by complex genomic rearrangements but the majority of the genes that are the target of these alterations remain unidentified. Cataloguing these target genes will provide useful insights into the disease etiology and may provide an opportunity to develop novel diagnostic and therapeutic interventions. High resolution genome wide copy number and matching expression data from 68 primary epithelial ovarian carcinomas of various histotypes was integrated to identify genes in regions of most frequent amplification with the strongest correlation with expression and copy number. Regions on chromosomes 3, 7, 8, and 20 were most frequently increased in copy number (> 40% of samples). Within these regions, 703/1370 (51%) unique gene expression probesets were differentially expressed when samples with gain were compared to samples without gain. 30% of these differentially expressed probesets also showed a strong positive correlation (r > or =0.6) between expression and copy number. We also identified 21 regions of high amplitude copy number gain, in which 32 known protein coding genes showed a strong positive correlation between expression and copy number. Overall, our data validates previously known ovarian cancer genes, such as ERBB2, and also identified novel potential drivers such as MYNN, PUF60 and TPX2.
Ramakrishna
Manasa
M
VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
Williams
Louise H
LH
Boyle
Samantha E
SE
Bearfoot
Jennifer L
JL
Sridhar
Anita
A
Speed
Terence P
TP
Gorringe
Kylie L
KL
Campbell
Ian G
IG
D018797:Cell Cycle Proteins / Q000235:genetics; D002875:Chromosomes; D004268:DNA-Binding Proteins; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D018734:Genes, erbB-2; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics*; D014157:Transcription Factors
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; C410903:MYNN protein, human; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C122167:TPX2 protein, human; D014157:Transcription Factors
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