{"doi":"10.1371/journal.pone.0260857","title":"Genome-wide host methylation profiling of anal and cervical carcinoma","abstract":"HPV infection results in changes in host gene methylation which, in turn, are thought to contribute to the neoplastic progression of HPV-associated cancers. The objective of this study was to identify joint and disease-specific genome-wide methylation changes in anal and cervical cancer as well as changes in high-grade pre-neoplastic lesions. Formalin-fixed paraffin-embedded (FFPE) anal tissues (n = 143; 99% HPV+) and fresh frozen cervical tissues (n = 28; 100% HPV+) underwent microdissection, DNA extraction, HPV genotyping, bisulfite modification, DNA restoration (FFPE) and analysis by the Illumina HumanMethylation450 Array. Differentially methylated regions (DMR; t test q<0.01, 3 consecutive significant CpG probes and mean Δβ methylation value>0.3) were compared between normal and cancer specimens in partial least squares (PLS) models and then used to classify anal or cervical intraepithelial neoplasia-3 (AIN3/CIN3). In AC, an 84-gene PLS signature (355 significant probes) differentiated normal anal mucosa (NM; n = 9) from AC (n = 121) while a 36-gene PLS signature (173 significant probes) differentiated normal cervical epithelium (n = 10) from CC (n = 9). The CC progression signature was validated using three independent publicly available datasets (n = 424 cases). The AC and CC progression PLS signatures were interchangeable in segregating normal, AIN3/CIN3 and AC and CC and were found to include 17 common overlapping hypermethylated genes. Moreover, these signatures segregated AIN3/CIN3 lesions similarly into cancer-like and normal-like categories. Distinct methylation changes occur across the genome during the progression of AC and CC with overall similar profiles and add to the evidence suggesting that HPV-driven oncogenesis may result in similar non-random methylomic events. Our findings may lead to identification of potential epigenetic drivers of HPV-associated cancers and also, of potential markers to identify higher risk pre-cancerous lesions.","journal":"PLoS ONE","year":2021,"id":189572,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9314,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":519674,"name":"Abidemi Ajidahun","orcid":"0000-0002-8731-8884","position":1,"is_corresponding":false},{"id":255361,"name":"Anders Berglund","orcid":"0000-0002-0393-3530","position":2,"is_corresponding":false},{"id":752294,"name":"Whitney Guerrero","orcid":"0000-0003-4826-5449","position":3,"is_corresponding":false},{"id":318018,"name":"Steven A. Eschrich","orcid":"0000-0002-9833-2788","position":4,"is_corresponding":false},{"id":671318,"name":"Ryan M. Putney","orcid":"0000-0002-0468-736X","position":5,"is_corresponding":false},{"id":244057,"name":"Anthony M. Magliocco","orcid":null,"position":6,"is_corresponding":false},{"id":752903,"name":"Bridget M. Riggs","orcid":null,"position":7,"is_corresponding":false},{"id":260978,"name":"Kathryn Winter","orcid":null,"position":8,"is_corresponding":false},{"id":684170,"name":"Jeff Simko","orcid":null,"position":9,"is_corresponding":false},{"id":69924,"name":"Jaffer A. Ajani","orcid":"0000-0001-9946-0629","position":10,"is_corresponding":false},{"id":276963,"name":"Chandan Guha","orcid":"0000-0002-1906-2186","position":11,"is_corresponding":false},{"id":752904,"name":"Gordon Okawara","orcid":null,"position":12,"is_corresponding":false},{"id":752295,"name":"Ibrahim Abdalla","orcid":"0000-0002-5052-1547","position":13,"is_corresponding":false},{"id":752905,"name":"M. Becker","orcid":null,"position":14,"is_corresponding":false},{"id":752906,"name":"Joseph F. Pizzolato","orcid":null,"position":15,"is_corresponding":false},{"id":305046,"name":"Christopher H. Crane","orcid":"0000-0001-5143-2784","position":16,"is_corresponding":false},{"id":442141,"name":"Kevin D. Brown","orcid":"0000-0003-3020-8964","position":17,"is_corresponding":false},{"id":519677,"name":"David Shibata","orcid":"0000-0002-5670-423X","position":18,"is_corresponding":false},{"id":695513,"name":"Erin M. Siegel","orcid":"0000-0003-1779-2510","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-18T23:49:18.604374Z","pmid":"34882728","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}