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

Nat Commun. 2013:4:1806. doi: 10.1038/ncomms2693.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / metabolism*
  • Cell Cycle / genetics*
  • Chromosome Aberrations
  • Chromosomes, Human / genetics
  • Databases, Genetic
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks / genetics*
  • Genes, Neoplasm / genetics*
  • Genome, Human / genetics
  • Genomic Instability
  • Humans
  • Lysosomal Membrane Proteins / metabolism
  • Meta-Analysis as Topic
  • Neoplasm Proteins / metabolism
  • Papillomaviridae / genetics*
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / virology
  • Reproducibility of Results
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology*
  • Virus Integration / genetics

Substances

  • Antiviral Agents
  • LAMP3 protein, human
  • Lysosomal Membrane Proteins
  • Neoplasm Proteins

Associated data

  • GEO/GSE26342
  • GEO/GSE27469