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. | PubMed

Alessia Gagliardi¹, Vanessa L Porter^1,2, Zusheng Zong¹, Reanne Bowlby¹, Emma Titmuss¹, Constance Namirembe³, Nicholas B Griner⁴, Hilary Petrello⁵, Jay Bowen⁵, Simon K Chan¹, Luka Culibrk¹, Teresa M Darragh⁶, Mark H Stoler⁷, Thomas C Wright⁸, Patee Gesuwan⁴, Maureen A Dyer⁹, Yussanne Ma¹, Karen L Mungall¹, Steven J M Jones^1,2, Carolyn Nakisige³, Karen Novik¹, Jackson Orem³, Martin Origa³, Julie M Gastier-Foster^5,10, Robert Yarchoan^11,12, Corey Casper¹³, Gordon B Mills¹⁴, Janet S Rader¹⁵, Akinyemi I Ojesina^16,17,18, Daniela S Gerhard⁴, Andrew J Mungall¹, Marco A Marra^19,20

1. Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada.
2. Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
3. Uganda Cancer Institute, Kampala, Uganda.
4. Office of Cancer Genomics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
5. Nationwide Children's Hospital, Columbus, OH, USA.
6. Department of Pathology, University of California at San Francisco, San Francisco, CA, USA.
7. Department of Pathology, University of Virginia, Charlottesville, VA, USA.
8. Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
9. Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
10. Departments of Pathology and Pediatrics, The Ohio State University, Columbus, OH, USA.
11. Office of HIV and AIDS Malignancy, National Cancer Institute, National Institues of Health, Bethesda, MD, USA.
12. HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
13. Infectious Disease Research Institute, Seattle, WA, USA.
14. Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
15. Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, USA.
16. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
17. O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.
18. HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
19. Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada. mmarra@bcgsc.ca.
20. Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada. mmarra@bcgsc.ca.

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.

Presented By Vanessa Porter | ORCID iD