| Summary: | <p>Abstract</p> <p>Background</p> <p>Copy number gains and amplifications are characteristic feature of cervical cancer (CC) genomes for which the underlying mechanisms are unclear. These changes may possess oncogenic properties by deregulating tumor-related genes. Gain of short arm of chromosome 5 (5p) is the most frequent karyotypic change in CC.</p> <p>Methods</p> <p>To examine the role of 5p gain, we performed a combination of single nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH), and gene expression analyses on invasive cancer and in various stages of CC progression.</p> <p>Results</p> <p>The SNP and FISH analyses revealed copy number increase (CNI) of 5p in 63% of invasive CC, which arises at later stages of precancerous lesions in CC development. We integrated chromosome 5 genomic copy number and gene expression data to identify key target over expressed genes as a consequence of 5p gain. One of the candidates identified was Drosha (<it>RNASEN</it>), a gene that is required in the first step of microRNA (miRNA) processing in the nucleus. Other 5p genes identified as targets of CNI play a role in DNA repair and cell cycle regulation (<it>BASP1</it>, <it>TARS</it>, <it>PAIP1</it>, <it>BRD9</it>, <it>RAD1</it>, <it>SKP2</it>, and <it>POLS</it>), signal transduction (<it>OSMR</it>), and mitochondrial oxidative phosphorylation (<it>NNT</it>, <it>SDHA</it>, and <it>NDUFS6</it>), suggesting that disruption of pathways involving these genes may contribute to CC progression.</p> <p>Conclusion</p> <p>Taken together, we demonstrate the power of integrating genomics data with expression data in deciphering tumor-related targets of CNI. Identification of 5p gene targets in CC denotes an important step towards biomarker development and forms a framework for testing as molecular therapeutic targets.</p>
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