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

  • Author(s): Gagliardi, Alessia
  • Porter, Vanessa L
  • Zong, Zusheng
  • Bowlby, Reanne
  • Titmuss, Emma
  • Namirembe, Constance
  • Griner, Nicholas B
  • Petrello, Hilary
  • Bowen, Jay
  • Chan, Simon K
  • Culibrk, Luka
  • Darragh, Teresa M
  • Stoler, Mark H
  • Wright, Thomas C
  • Gesuwan, Patee
  • Dyer, Maureen A
  • Ma, Yussanne
  • Mungall, Karen L
  • Jones, Steven JM
  • Nakisige, Carolyn
  • Novik, Karen
  • Orem, Jackson
  • Origa, Martin
  • Gastier-Foster, Julie M
  • Yarchoan, Robert
  • Casper, Corey
  • Mills, Gordon B
  • Rader, Janet S
  • Ojesina, Akinyemi I
  • Gerhard, Daniela S
  • Mungall, Andrew J
  • Marra, Marco A
  • et al.
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.

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