{"doi":"10.1002/cncr.33542","title":"Relationships between highly recurrent tumor suppressor alterations in 489 leiomyosarcomas","abstract":"BACKGROUND: Leiomyosarcoma (LMS) is the most common soft tissue and uterine sarcoma, but no standard therapy is available for recurrent or metastatic LMS. TP53, p16/RB1, and PI3K/mTOR pathway dysregulations are recurrent events, and some LMS express estrogen receptor (ER) and/or progesterone receptor (PR). To characterize relationships between these pathway perturbations, the authors evaluated protein expression in soft tissue and uterine nonprimary leiomyosarcoma (np-LMS), including local recurrences and distant metastases. METHODS: TP53, RB1, p16, and PTEN expression aberrations were determined by immunohistochemistry (IHC) in tissue microarrays (TMAs) from 227 np-LMS and a comparison group of 262 primary leiomyosarcomas (p-LMS). Thirty-five of the np-LMS had a matched p-LMS specimen in the TMAs. Correlative studies included differentiation scoring, ER and PR IHC, and CDKN2A/p16 fluorescence in situ hybridization. RESULTS: Dysregulation of TP53, p16/RB1, and PTEN was demonstrated in 90%, 95%, and 41% of np-LMS, respectively. PTEN inactivation was more common in soft tissue np-LMS than uterine np-LMS (55% vs 31%; P = .0005). Moderate-strong ER expression was more common in uterine np-LMS than soft tissue np-LMS (50% vs 7%; P < .0001). Co-inactivation of TP53 and RB1 was found in 81% of np-LMS and was common in both soft tissue and uterine np-LMS (90% and 74%, respectively). RB1, p16, and PTEN aberrations were nearly always conserved in p-LMS and np-LMS from the same patients. CONCLUSIONS: These studies show that nearly all np-LMS have TP53 and/or RB1 aberrations. Therefore, therapies targeting cell cycle and DNA damage checkpoint vulnerabilities should be prioritized for evaluations in LMS.","journal":"Cancer","year":2021,"id":165707,"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":35,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"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":673581,"name":"Meijun Z. Lundberg","orcid":"0009-0009-5601-8035","position":1,"is_corresponding":false},{"id":668188,"name":"Elizabeth G. Demicco","orcid":"0000-0003-4144-8824","position":2,"is_corresponding":false},{"id":689543,"name":"Joanna Przybył","orcid":"0000-0002-8162-5226","position":3,"is_corresponding":false},{"id":554532,"name":"Magdalena Matusiak","orcid":"0000-0002-8201-1621","position":4,"is_corresponding":false},{"id":689544,"name":"Frédéric Chibon","orcid":"0000-0002-6548-2181","position":5,"is_corresponding":false},{"id":309158,"name":"Davis R. Ingram","orcid":"0000-0001-5967-1501","position":6,"is_corresponding":false},{"id":59691,"name":"Jason L. Hornick","orcid":"0000-0001-6475-8345","position":7,"is_corresponding":false},{"id":105064,"name":"Wei‐Lien Wang","orcid":"0000-0001-8809-4424","position":8,"is_corresponding":false},{"id":320533,"name":"Sebastian Bauer","orcid":"0000-0001-5949-8120","position":9,"is_corresponding":false},{"id":604762,"name":"Laurence H. Baker","orcid":"0009-0009-2663-2536","position":10,"is_corresponding":false},{"id":13708,"name":"Alexander J. Lazar","orcid":"0000-0002-6395-4499","position":11,"is_corresponding":false},{"id":34868,"name":"Matt van de Rijn","orcid":"0000-0002-1909-9739","position":12,"is_corresponding":false},{"id":473190,"name":"Adrián Mariño‐Enríquez","orcid":"0000-0002-7680-9901","position":13,"is_corresponding":false},{"id":35282,"name":"Jonathan A. Fletcher","orcid":"0000-0002-5109-2588","position":14,"is_corresponding":false},{"id":260064,"name":"Inga‐Marie Schaefer","orcid":"0000-0001-9710-5500","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-18T23:45:40.838485Z","pmid":"33788262","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":[]}