title: Gene network reconstruction reveals cell cycle and antiviral genes as major drivers of cervical cancer.
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.
authors: Instituto de Imunogenética-Associação Fundo de Incentivo à Pesquisa (IGEN-AFIP), São Paulo, São Paulo, Brazil.
authors: Karina L
authors: KL
authors: Mine
authors: Natalia
authors: N
authors: Shulzhenko
authors: Anatoly
authors: A
authors: Yambartsev
authors: Mark
authors: M
authors: Rochman
authors: Gerdine F O
authors: GF
authors: Sanson
authors: Malin
authors: M
authors: Lando
authors: Sudhir
authors: S
authors: Varma
authors: Jeff
authors: J
authors: Skinner
authors: Natalia
authors: N
authors: Volfovsky
authors: Tao
authors: T
authors: Deng
authors: Sylvia M F
authors: SM
authors: Brenna
authors: Carmen R N
authors: CR
authors: Carvalho
authors: Julisa C L
authors: JC
authors: Ribalta
authors: Michael
authors: M
authors: Bustin
authors: Polly
authors: P
authors: Matzinger
authors: Ismael D C G
authors: ID
authors: Silva
authors: Heidi
authors: H
authors: Lyng
authors: Maria
authors: M
authors: Gerbase-DeLima
authors: Andrey
authors: A
authors: Morgun
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics*; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks / Q000235:genetics*; D052138:Genes, Neoplasm / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D042822:Genomic Instability; D006801:Humans; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D015201:Meta-Analysis as Topic; D009363:Neoplasm Proteins / Q000378:metabolism; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000235:genetics / Q000821:virology; D015203:Reproducibility of Results; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D016662:Virus Integration / Q000235:genetics; D059666:Lysosomal-Associated Membrane Protein 3
chemical_list: D000998:Antiviral Agents; D051907:Lysosomal Membrane Proteins; D009363:Neoplasm Proteins; C114233:LAMP3 protein, human; D059666:Lysosomal-Associated Membrane Protein 3
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