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Integrative genomics analysis of chromosome 5p gain in cervical cancer reveals target over-expressed genes, including Drosha

BACKGROUND: 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...

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Autores principales: Scotto, Luigi, Narayan, Gopeshwar, Nandula, Subhadra V, Subramaniyam, Shivakumar, Kaufmann, Andreas M, Wright, Jason D, Pothuri, Bhavana, Mansukhani, Mahesh, Schneider, Achim, Arias-Pulido, Hugo, Murty, Vundavalli V
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440550/
https://www.ncbi.nlm.nih.gov/pubmed/18559093
http://dx.doi.org/10.1186/1476-4598-7-58
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author Scotto, Luigi
Narayan, Gopeshwar
Nandula, Subhadra V
Subramaniyam, Shivakumar
Kaufmann, Andreas M
Wright, Jason D
Pothuri, Bhavana
Mansukhani, Mahesh
Schneider, Achim
Arias-Pulido, Hugo
Murty, Vundavalli V
author_facet Scotto, Luigi
Narayan, Gopeshwar
Nandula, Subhadra V
Subramaniyam, Shivakumar
Kaufmann, Andreas M
Wright, Jason D
Pothuri, Bhavana
Mansukhani, Mahesh
Schneider, Achim
Arias-Pulido, Hugo
Murty, Vundavalli V
author_sort Scotto, Luigi
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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 (RNASEN), 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 (BASP1, TARS, PAIP1, BRD9, RAD1, SKP2, and POLS), signal transduction (OSMR), and mitochondrial oxidative phosphorylation (NNT, SDHA, and NDUFS6), suggesting that disruption of pathways involving these genes may contribute to CC progression. CONCLUSION: 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.
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spelling pubmed-24405502008-06-27 Integrative genomics analysis of chromosome 5p gain in cervical cancer reveals target over-expressed genes, including Drosha Scotto, Luigi Narayan, Gopeshwar Nandula, Subhadra V Subramaniyam, Shivakumar Kaufmann, Andreas M Wright, Jason D Pothuri, Bhavana Mansukhani, Mahesh Schneider, Achim Arias-Pulido, Hugo Murty, Vundavalli V Mol Cancer Research BACKGROUND: 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. METHODS: 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. RESULTS: 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 (RNASEN), 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 (BASP1, TARS, PAIP1, BRD9, RAD1, SKP2, and POLS), signal transduction (OSMR), and mitochondrial oxidative phosphorylation (NNT, SDHA, and NDUFS6), suggesting that disruption of pathways involving these genes may contribute to CC progression. CONCLUSION: 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. BioMed Central 2008-06-17 /pmc/articles/PMC2440550/ /pubmed/18559093 http://dx.doi.org/10.1186/1476-4598-7-58 Text en Copyright © 2008 Scotto et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Scotto, Luigi
Narayan, Gopeshwar
Nandula, Subhadra V
Subramaniyam, Shivakumar
Kaufmann, Andreas M
Wright, Jason D
Pothuri, Bhavana
Mansukhani, Mahesh
Schneider, Achim
Arias-Pulido, Hugo
Murty, Vundavalli V
Integrative genomics analysis of chromosome 5p gain in cervical cancer reveals target over-expressed genes, including Drosha
title Integrative genomics analysis of chromosome 5p gain in cervical cancer reveals target over-expressed genes, including Drosha
title_full Integrative genomics analysis of chromosome 5p gain in cervical cancer reveals target over-expressed genes, including Drosha
title_fullStr Integrative genomics analysis of chromosome 5p gain in cervical cancer reveals target over-expressed genes, including Drosha
title_full_unstemmed Integrative genomics analysis of chromosome 5p gain in cervical cancer reveals target over-expressed genes, including Drosha
title_short Integrative genomics analysis of chromosome 5p gain in cervical cancer reveals target over-expressed genes, including Drosha
title_sort integrative genomics analysis of chromosome 5p gain in cervical cancer reveals target over-expressed genes, including drosha
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440550/
https://www.ncbi.nlm.nih.gov/pubmed/18559093
http://dx.doi.org/10.1186/1476-4598-7-58
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