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

Autor: Gagliardi A; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada., Porter VL; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada., Zong Z; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada., Bowlby R; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada., Titmuss E; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada., Namirembe C; Uganda Cancer Institute, Kampala, Uganda., Griner NB; Office of Cancer Genomics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Petrello H; Nationwide Children's Hospital, Columbus, OH, USA., Bowen J; Nationwide Children's Hospital, Columbus, OH, USA., Chan SK; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada., Culibrk L; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada., Darragh TM; Department of Pathology, University of California at San Francisco, San Francisco, CA, USA., Stoler MH; Department of Pathology, University of Virginia, Charlottesville, VA, USA., Wright TC; Department of Pathology and Cell Biology, Columbia University, New York, NY, USA., Gesuwan P; Office of Cancer Genomics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Dyer MA; Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Ma Y; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada., Mungall KL; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada., Jones SJM; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada., Nakisige C; Uganda Cancer Institute, Kampala, Uganda., Novik K; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada., Orem J; Uganda Cancer Institute, Kampala, Uganda., Origa M; Uganda Cancer Institute, Kampala, Uganda., Gastier-Foster JM; Nationwide Children's Hospital, Columbus, OH, USA.; Departments of Pathology and Pediatrics, The Ohio State University, Columbus, OH, USA., Yarchoan R; Office of HIV and AIDS Malignancy, National Cancer Institute, National Institues of Health, Bethesda, MD, USA.; HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Casper C; Infectious Disease Research Institute, Seattle, WA, USA., Mills GB; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA., Rader JS; Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, USA., Ojesina AI; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.; O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.; HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA., Gerhard DS; Office of Cancer Genomics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Mungall AJ; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada., Marra MA; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada. mmarra@bcgsc.ca.; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada. mmarra@bcgsc.ca.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2020 Aug; Vol. 52 (8), pp. 800-810. Date of Electronic Publication: 2020 Aug 03.
DOI: 10.1038/s41588-020-0673-7
Abstrakt: 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.
Databáze: MEDLINE