Gene network reconstruction reveals cell cycle and antiviral genes as major drivers of cervical cancer

Karina L. Mine, Natalia Shulzhenko, Anatoly Yambartsev, Mark Rochman, Gerdine F. O. Sanson, Malin Lando, Sudhir Varma, Jeff Skinner, Natalia Volfovsky, Tao Deng, Sylvia M. F. Brenna, Carmen R. N. Carvalho, Julisa C. L. Ribalta, Michael Bustin, Polly Matzinger, Ismael D. C. G. Silva, Heidi Lyng, Maria Gerbase-DeLima and Andrey Morgun ()
Additional contact information
Karina L. Mine: Instituto de Imunogenética—Associação Fundo de Incentivo à Pesquisa (IGEN-AFIP)
Natalia Shulzhenko: Instituto de Imunogenética—Associação Fundo de Incentivo à Pesquisa (IGEN-AFIP)
Anatoly Yambartsev: Institute of Mathematics and Statistics, University of Sao Paulo
Mark Rochman: Protein Section, Laboratory of Metabolism, Center for Cancer Research, NCI, NIH
Gerdine F. O. Sanson: Instituto de Imunogenética—Associação Fundo de Incentivo à Pesquisa (IGEN-AFIP)
Malin Lando: Norwegian Radium Hospital
Sudhir Varma: Bioinformatics and Computational Biosciences Branch, NIAID, NIH
Jeff Skinner: Bioinformatics and Computational Biosciences Branch, NIAID, NIH
Natalia Volfovsky: Advanced Biomedical Computing Center, SAIC-Frederick, Inc
Tao Deng: Protein Section, Laboratory of Metabolism, Center for Cancer Research, NCI, NIH
Sylvia M. F. Brenna: Medical School of Universidade Cidade de São Paulo (UNICID)
Carmen R. N. Carvalho: Universidade Federal de São Paulo
Julisa C. L. Ribalta: Universidade Federal de São Paulo
Michael Bustin: Protein Section, Laboratory of Metabolism, Center for Cancer Research, NCI, NIH
Polly Matzinger: Laboratory of Cellular and Molecular Immunology, NIAID, NIH
Ismael D. C. G. Silva: Universidade Federal de São Paulo
Heidi Lyng: Norwegian Radium Hospital
Maria Gerbase-DeLima: Instituto de Imunogenética—Associação Fundo de Incentivo à Pesquisa (IGEN-AFIP)
Andrey Morgun: Instituto de Imunogenética—Associação Fundo de Incentivo à Pesquisa (IGEN-AFIP)

Nature Communications, 2013, vol. 4, issue 1, 1-11

Abstract: Abstract 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.

Date: 2013
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DOI: 10.1038/ncomms2693

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