{"doi":"10.3390/cancers14174199","title":"A Pan-Cancer Assessment of RB1/TP53 Co-Mutations","abstract":"Nearly all tumors have multiple mutations in cancer-causing genes. Which of these mutations act in tandem with other mutations to drive malignancy and also provide therapeutic vulnerability? To address this fundamental question, we conducted a pan-cancer screen of co-mutation enrichment (looking for two genes mutated together in the same tumor at a statistically significant rate) using the AACR-GENIE 11.0 data (AACR, Philadelphia, PA, USA). We developed a web tool for users to review results and perform ad hoc analyses. From our screen, we identified a number of such co-mutations and their associated lineages. Here, we focus on the RB1/TP53 co-mutation, which we discovered was the most frequently observed co-mutation across diverse cancer types, with particular enrichment in small cell carcinomas, neuroendocrine carcinomas, and sarcomas. Furthermore, in many cancers with a substantial fraction of co-mutant tumors, the presence of concurrent RB1/TP53 mutations is associated with poor clinical outcomes. From pan-cancer cell line multi-omics and functional screening datasets, we identified many targetable co-mutant-specific molecular alterations. Overall, our analyses revealed the prevalence, cancer type-specificity, clinical significance, and therapeutic vulnerabilities of the RB1/TP53 co-mutation in the pan-cancer landscape and provide a roadmap forward for future clinical translational research.","journal":"Cancers","year":2022,"id":257800,"datarank":0.44166584687496613,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.0,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9103,"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":262195,"name":"Ralph J. DeBerardinis","orcid":"0000-0002-2705-7432","position":1,"is_corresponding":false},{"id":808272,"name":"Guanghua Xiao","orcid":"0000-0002-6738-7014","position":2,"is_corresponding":false},{"id":71347,"name":"John D. Minna","orcid":"0000-0002-7776-0767","position":3,"is_corresponding":false},{"id":326811,"name":"Yang Xie","orcid":"0000-0001-9456-1762","position":4,"is_corresponding":false},{"id":273494,"name":"Ling Cai","orcid":"0000-0002-8592-5269","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:25:34.440699Z","pmid":"36077736","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":[]}