{"doi":"10.1016/j.clgc.2021.02.002","title":"TERT Gene Fusions Characterize a Subset of Metastatic Leydig Cell Tumors","abstract":"OBJECTIVE: Metastatic Leydig cell tumors (LCT) are rare, difficult-to-treat malignancies without known underlying molecular-genetic events. An index case of metastatic LCT showed an LDLR-TERT gene fusion upon routine genetic profiling for detection of therapeutic targets, which was then followed by an investigation into a cohort of additional LCTs. PATIENTS AND METHODS: Twenty-nine LCT (27 male and 2 female patients) were profiled using next-generation sequencing and immunohistochemistry. RESULTS: TERT gene fusions were detected only in testicular metastatic LCTs, in 3 of 7 successfully analyzed cases (RMST:TERT, LDLR:TERT, and B4GALT5:TERT). TOP1 and CCND3 amplifications were identified in the case with a B4GALT5:TERT fusion. A TP53 mutation was detected in 1 metastatic tumor without a TERT fusion. Five primary (4 testicular and 1 ovarian) LCTs showed multiple gene amplifications, without a consistent pattern. A single metastatic ovarian LCT showed BAP1 mutation and copy number amplifications affecting the NPM1, PCM1, and SS18 genes. At the protein level, 4 of 7 metastatic and 6 of 10 primary testicular LCTs overexpressed Topo1. Androgen receptor was overexpressed in 10 of 13 primary testicular tumors and 2 of 5 metastatic testicular LCTs (without detectable ARv7 messenger RNA or ARv7 protein). Only 1 metastatic testicular LCT exhibited a high tumor mutational burden; all tested cases were microsatellite instability stable and did not express programmed cell death ligand 1. CONCLUSIONS: Our study for the first time identified TERT gene fusions as a main genetic alteration and a potential therapeutic target in metastatic LCTs. Topo1 and androgen receptor may guide decisions on chemotherapy and/or hormone therapy for selected individual patients.","journal":"Clinical Genitourinary Cancer","year":2021,"id":178172,"datarank":0.4493598410330987,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.0,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7367,"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":474199,"name":"Zoran Gatalica","orcid":null,"position":1,"is_corresponding":false},{"id":723330,"name":"Ondřej Hes","orcid":"0000-0002-3236-3127","position":2,"is_corresponding":false},{"id":723331,"name":"Faruk Skenderi","orcid":"0000-0002-2200-354X","position":3,"is_corresponding":false},{"id":329927,"name":"Markku Miettinen","orcid":"0000-0002-3282-8107","position":4,"is_corresponding":false},{"id":723887,"name":"Elma Contreras","orcid":null,"position":5,"is_corresponding":false},{"id":254337,"name":"Joanne Xiu","orcid":"0000-0001-8744-5827","position":6,"is_corresponding":false},{"id":723332,"name":"Michelle Ellis","orcid":"0000-0002-6517-9932","position":7,"is_corresponding":false},{"id":723888,"name":"Elena Florento","orcid":null,"position":8,"is_corresponding":false},{"id":723889,"name":"Semir Vranić","orcid":null,"position":9,"is_corresponding":false},{"id":723333,"name":"Jeffrey Swensen","orcid":"0000-0002-8204-4220","position":10,"is_corresponding":false},{"id":384900,"name":"Božo Krušlin","orcid":"0000-0002-0480-1687","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:47:36.112170Z","pmid":"33741265","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":[]}