{"doi":"10.1101/2022.08.10.503516","title":"Widespread perturbation of ETS factor binding sites in cancer","abstract":"Abstract Although >90% of somatic mutations reside in non-coding regions, few have been reported as cancer drivers. To predict driver non-coding variants (NCVs), we present a novel transcription factor (TF)-aware burden test (TFA-BT) based on a model of coherent TF function in promoters. We applied our TFA-BT to NCVs from the Pan-Cancer Analysis of Whole Genomes cohort and predicted 2,555 driver NCVs in the promoters of 813 genes across 20 cancer-types. These genes are enriched in cancer-related gene ontologies, essential genes, and genes associated with cancer prognosis. We found that 765 candidate driver NCVs alter transcriptional activity, 510 lead to differential binding of TF-cofactor regulatory complexes, and that they primarily impact the binding of ETS factors. Finally, we show that different NCVs within a promoter often affect transcriptional activity through shared mechanisms. Our integrated computational and experimental approach shows that cancer NCVs are widespread and that ETS factors are commonly disrupted.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":310640,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":575128,"name":"Heather Hook","orcid":null,"position":1,"is_corresponding":false},{"id":574413,"name":"David A. Bray","orcid":"0009-0008-7453-3818","position":2,"is_corresponding":false},{"id":730977,"name":"Daniel Berenzy","orcid":"0000-0001-8695-8903","position":3,"is_corresponding":false},{"id":304497,"name":"Devlin C. Moyer","orcid":"0000-0002-6997-9531","position":4,"is_corresponding":false},{"id":1006689,"name":"Ming Yin","orcid":"0000-0001-7917-6647","position":5,"is_corresponding":false},{"id":1007060,"name":"AT Labadorf","orcid":null,"position":6,"is_corresponding":false},{"id":3034,"name":"Ryan Tewhey","orcid":"0000-0002-4607-8001","position":7,"is_corresponding":false},{"id":56375,"name":"Trevor Siggers","orcid":"0000-0002-8039-7639","position":8,"is_corresponding":false},{"id":565326,"name":"JI Fuxman Bass","orcid":null,"position":9,"is_corresponding":false},{"id":336758,"name":"Sebastian Carrasco Pro","orcid":"0000-0003-3388-3789","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-19T00:33:24.451129Z","pmid":null,"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":[]}