{"doi":"10.1016/j.celrep.2024.114764","title":"Integrative identification of non-coding regulatory regions driving metastatic prostate cancer","abstract":"Large-scale sequencing efforts have been undertaken to understand the mutational landscape of the coding genome. However, the vast majority of variants occur within non-coding genomic regions. We designed an integrative computational and experimental framework to identify recurrently mutated non-coding regulatory regions that drive tumor progression. Applying this framework to sequencing data from a large prostate cancer patient cohort revealed a large set of candidate drivers. We used (1) in silico analyses, (2) massively parallel reporter assays, and (3) in vivo CRISPR interference screens to systematically validate metastatic castration-resistant prostate cancer (mCRPC) drivers. One identified enhancer region, GH22I030351, acts on a bidirectional promoter to simultaneously modulate expression of the U2-associated splicing factor SF3A1 and chromosomal protein CCDC157. SF3A1 and CCDC157 promote tumor growth in vivo. We nominated a number of transcription factors, notably SOX6, to regulate expression of SF3A1 and CCDC157. Our integrative approach enables the systematic detection of non-coding regulatory regions that drive human cancers.","journal":"Cell Reports","year":2024,"id":466371,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7978,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1175396,"name":"Ruhollah Moussavi-Baygi","orcid":null,"position":1,"is_corresponding":false},{"id":1175397,"name":"Heather Karner","orcid":null,"position":2,"is_corresponding":false},{"id":52777,"name":"Mehran Karimzadeh","orcid":"0000-0002-7324-6074","position":3,"is_corresponding":false},{"id":798479,"name":"Hassan Yousefi","orcid":null,"position":4,"is_corresponding":false},{"id":528686,"name":"Sean M. Lee","orcid":"0000-0002-9897-3315","position":5,"is_corresponding":false},{"id":315085,"name":"Kristle Garcia","orcid":"0000-0002-9868-8397","position":6,"is_corresponding":false},{"id":630183,"name":"Tanvi Joshi","orcid":"0009-0001-5051-7927","position":7,"is_corresponding":false},{"id":270755,"name":"Keyi Yin","orcid":"0000-0002-4470-518X","position":8,"is_corresponding":false},{"id":239637,"name":"Albertas Navickas","orcid":"0000-0003-0016-2643","position":9,"is_corresponding":false},{"id":319827,"name":"Luke A. Gilbert","orcid":"0000-0001-5854-0825","position":10,"is_corresponding":false},{"id":1175161,"name":"Bo Wang","orcid":"0009-0004-0989-2225","position":11,"is_corresponding":false},{"id":239639,"name":"Hosseinali Asgharian","orcid":"0000-0001-7085-5045","position":12,"is_corresponding":false},{"id":259327,"name":"Felix Y. Feng","orcid":"0000-0002-0963-7687","position":13,"is_corresponding":false},{"id":43301,"name":"Hani Goodarzi","orcid":"0000-0002-9648-8949","position":14,"is_corresponding":false},{"id":823021,"name":"Brian Woo","orcid":null,"position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T02:04:54.606394Z","pmid":"39276353","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":[]}