Analysis of Ugandan cervical carcinomas identifies human papillomavirus clade-specific epigenome and transcriptome landscapes

Nat Genet. 2020 Aug;52(8):800-810. doi: 10.1038/s41588-020-0673-7. Epub 2020 Aug 3.

Abstract

Cervical cancer is the most common cancer affecting sub-Saharan African women and is prevalent among HIV-positive (HIV+) individuals. No comprehensive profiling of cancer genomes, transcriptomes or epigenomes has been performed in this population thus far. We characterized 118 tumors from Ugandan patients, of whom 72 were HIV+, and performed extended mutation analysis on an additional 89 tumors. We detected human papillomavirus (HPV)-clade-specific differences in tumor DNA methylation, promoter- and enhancer-associated histone marks, gene expression and pathway dysregulation. Changes in histone modification at HPV integration events were correlated with upregulation of nearby genes and endogenous retroviruses.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • DNA Methylation / genetics
  • Epigenome / genetics*
  • Female
  • Humans
  • Middle Aged
  • Papillomaviridae / pathogenicity*
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / virology*
  • Promoter Regions, Genetic / genetics
  • Signal Transduction / genetics
  • Transcriptome / genetics*
  • Uganda
  • Up-Regulation / genetics
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / virology*