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Mine K.L.,Institute Imunogenetica Associacao Fundo Of Incentivo A Pesquisa | Mine K.L.,Federal University of Sao Paulo | Shulzhenko N.,Institute Imunogenetica Associacao Fundo Of Incentivo A Pesquisa | Shulzhenko N.,U.S. National Institutes of Health | And 22 more authors.
Nature Communications | Year: 2013

Although human papillomavirus was identified as an aetiological factor in cervical cancer, the key human gene drivers of this disease remain unknown. Here we apply an unbiased approach integrating gene expression and chromosomal aberration data. In an independent group of patients, we reconstruct and validate a gene regulatory meta-network, and identify cell cycle and antiviral genes that constitute two major subnetworks upregulated in tumour samples. These genes are located within the same regions as chromosomal amplifications, most frequently on 3q. We propose a model in which selected chromosomal gains drive activation of antiviral genes contributing to episomal virus elimination, which synergizes with cell cycle dysregulation. These findings may help to explain the paradox of episomal human papillomavirus decline in women with invasive cancer who were previously unable to clear the virus. © 2013 Macmillan Publishers Limited. All rights reserved. Source

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