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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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