{"doi":"10.21203/rs.3.rs-199044/v1","title":"A systematic genome-wide mapping of oncogenic mutation selection during CRISPR-Cas9 genome editing","abstract":"Abstract Recent studies have reported that genome editing by CRISPR–Cas9 induces a DNA damage response mediated by p53 in primary cells hampering their growth. This could lead to a selection of cells with pre-existing p53 mutations. In this study, employing an integrated computational and experimental framework, we systematically investigated the possibility of selection of additional cancer driver mutations during CRISPR-Cas9 gene editing. We first confirm the previous findings of the selection for pre-existing p53 mutations by CRISPR-Cas9. We next demonstrate that similar to p53 , wildtype KRAS may also hamper the growth of Cas9-edited cells, potentially conferring a selective advantage to pre-existing KRAS -mutant cells. These selective effects are widespread, extending across cell-types and methods of CRISPR-Cas9 delivery and the strength of selection depends on the sgRNA sequence and the gene being edited. The selection for pre-existing p53 or KRAS mutations may confound CRISPR-Cas9 screens in cancer cells and more importantly, calls for monitoring patients undergoing CRISPR-Cas9-based editing for clinical therapeutics for pre-existing p53 and KRAS mutations.","journal":"Research Square","year":2021,"id":229635,"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":0.9464,"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":834679,"name":"Karina Guerra","orcid":null,"position":1,"is_corresponding":false},{"id":107917,"name":"Kuoyuan Cheng","orcid":"0000-0001-8118-5243","position":2,"is_corresponding":false},{"id":18442,"name":"Mark D.M. Leiserson","orcid":"0000-0002-1034-4363","position":3,"is_corresponding":false},{"id":679699,"name":"Prashant Jain","orcid":"0000-0001-7179-9874","position":4,"is_corresponding":false},{"id":567677,"name":"Anagha Deshpande","orcid":"0000-0002-5653-2837","position":5,"is_corresponding":false},{"id":834502,"name":"David J. D. Wilson","orcid":"0000-0002-0007-4486","position":6,"is_corresponding":false},{"id":457253,"name":"Bríd M. Ryan","orcid":"0000-0003-0038-131X","position":7,"is_corresponding":false},{"id":594578,"name":"Ji Luo","orcid":"0000-0001-9709-7192","position":8,"is_corresponding":false},{"id":242052,"name":"Ze’ev A. Ronai","orcid":"0000-0002-3859-0400","position":9,"is_corresponding":false},{"id":3194,"name":"Joo Sang Lee","orcid":"0000-0001-8564-0848","position":10,"is_corresponding":false},{"id":259809,"name":"Aniruddha J. Deshpande","orcid":"0000-0002-5240-9356","position":11,"is_corresponding":false},{"id":3227,"name":"Eytan Ruppin","orcid":"0000-0002-7862-3940","position":12,"is_corresponding":false},{"id":3207,"name":"Sanju Sinha","orcid":"0000-0002-2688-0603","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:55:01.675482Z","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":[]}