Analysis of Ugandan cervical carcinomas identifies human papillomavirus clade–specific epigenome and transcriptome landscapes
Alessia Gagliardi, Vanessa Porter, Zusheng Zong, Reanne Bowlby, Emma Titmuss, Constance Namirembe, Nicholas B. Griner, Hilary Petrello, Jay Bowen, Simon K. Chan, Luka Culibrk, Teresa M. Darragh, Mark H. Stoler, Thomas C. Wright, Patee Gesuwan, Maureen A. Dyer, Yussanne Ma, Karen Mungall, Steven J.M. Jones, Carolyn Nakisige, Karen Novik, Jackson Orem, Martin Origa, Julie M. Gastier‐Foster, Robert Yarchoan, Corey Casper, Gordon B. Mills, Janet S. Rader, Akinyemi I. Ojesina, Daniela S. Gerhard, Andrew J. Mungall, Marco A. Marra
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. Genomic analysis of 118 cervical tumors from Ugandan individuals identifies HPV-clade-specific differences in tumor DNA methylation, regulatory-region-associated histone marks, gene expression and pathway dysregulation.