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

TitleGene network reconstruction reveals cell cycle and antiviral genes as major drivers of cervical cancer.
Publication TypeJournal Article
Year of Publication2013
AuthorsMine KL, Shulzhenko N, Yambartsev A, Rochman M, Sanson GFO, Lando M, Varma S, Skinner J, Volfovsky N, Deng T, Brenna SMF, Carvalho CRN, Ribalta JCL, Bustin M, Matzinger P, Silva IDCG, Lyng H, Gerbase-DeLima M, Morgun A
JournalNature communications
Volume4
Pagination1806
Date Published2013
ISSN2041-1723
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.

DOI10.1038/ncomms2693
Alternate JournalNat Commun