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

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

Author Mine, Karina L. Autor UNIFESP Google Scholar
Shulzhenko, Natalia Google Scholar
Yambartsev, Anatoly Google Scholar
Rochman, Mark Google Scholar
Sanson, Gerdine F. O. Google Scholar
Lando, Malin Google Scholar
Varma, Sudhir Google Scholar
Skinner, Jeff Google Scholar
Volfovsky, Natalia Google Scholar
Deng, Tao Google Scholar
Brenna, Sylvia M. F. Google Scholar
Carvalho, Carmen R. N. Autor UNIFESP Google Scholar
Ribalta, Julisa C. L. Autor UNIFESP Google Scholar
Bustin, Michael Google Scholar
Matzinger, Polly Google Scholar
Silva, Ismael D. C. G. Autor UNIFESP Google Scholar
Lyng, Heidi Google Scholar
Gerbase-DeLima, Maria Autor UNIFESP Google Scholar
Morgun, Andrey Google Scholar
Institution Inst Imunogenet Assoc Fundo Incent Pesquisa IGEN
Universidade Federal de São Paulo (UNIFESP)
Oregon State Univ
Universidade de São Paulo (USP)
Norwegian Radium Hosp
SAIC Frederick Inc
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.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
AFIP (Associacao Fundo de Incentivo Psicofarmacologia), São Paulo, Brazil
Intramural Research Program of the NIAID, NIH
Oregon State University, OR, USA
Date 2013-05-01
Published in Nature Communications. London: Nature Publishing Group, v. 4, 11 p., 2013.
ISSN 2041-1723 (Sherpa/Romeo, impact factor)
Publisher Nature Publishing Group
Extent 11
Access rights Closed access
Type Article
Web of Science ID WOS:000320589900002

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