1. Analysis of Ugandan cervical carcinomas identifies human papillomavirus clade-specific epigenome and transcriptome landscapes.
- Author
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Gagliardi A, Porter VL, Zong Z, Bowlby R, Titmuss E, Namirembe C, Griner NB, Petrello H, Bowen J, Chan SK, Culibrk L, Darragh TM, Stoler MH, Wright TC, Gesuwan P, Dyer MA, Ma Y, Mungall KL, Jones SJM, Nakisige C, Novik K, Orem J, Origa M, Gastier-Foster JM, Yarchoan R, Casper C, Mills GB, Rader JS, Ojesina AI, Gerhard DS, Mungall AJ, and Marra MA
- Subjects
- Adult, Aged, DNA Methylation genetics, Female, Humans, Middle Aged, Promoter Regions, Genetic genetics, Signal Transduction genetics, Uganda, Up-Regulation genetics, Epigenome genetics, Papillomaviridae pathogenicity, Papillomavirus Infections genetics, Papillomavirus Infections virology, Transcriptome genetics, Uterine Cervical Neoplasms genetics, Uterine Cervical Neoplasms virology
- 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.- Published
- 2020
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