{"doi":"10.3390/cancers14184506","title":"The Effect of Atm Loss on Radiosensitivity of a Primary Mouse Model of Pten-Deleted Brainstem Glioma","abstract":"Diffuse midline gliomas arise in the brainstem and other midline brain structures and cause a large proportion of childhood brain tumor deaths. Radiation therapy is the most effective treatment option, but these tumors ultimately progress. Inhibition of the phosphoinositide-3-kinase (PI3K)-like kinase, ataxia–telangiectasia mutated (ATM), which orchestrates the cellular response to radiation-induced DNA damage, may enhance the efficacy of radiation therapy. Diffuse midline gliomas in the brainstem contain loss-of-function mutations in the tumor suppressor PTEN, or functionally similar alterations in the phosphoinositide-3-kinase (PI3K) pathway, at moderate frequency. Here, we sought to determine if ATM inactivation could radiosensitize a primary mouse model of brainstem glioma driven by Pten loss. Using Cre/loxP recombinase technology and the RCAS/TVA retroviral gene delivery system, we established a mouse model of brainstem glioma driven by Pten deletion. We find that Pten-null brainstem gliomas are relatively radiosensitive at baseline. In addition, we show that deletion of Atm in the tumor cells does not extend survival of mice bearing Pten-null brainstem gliomas after focal brain irradiation. These results characterize a novel primary mouse model of PTEN-mutated brainstem glioma and provide insights into the mechanism of radiosensitization by ATM deletion, which may guide the design of future clinical trials.","journal":"Cancers","year":2022,"id":266723,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9422,"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":927296,"name":"María E. Guerra-García","orcid":null,"position":1,"is_corresponding":false},{"id":491682,"name":"Lixia Luo","orcid":"0000-0002-8413-0501","position":2,"is_corresponding":false},{"id":491684,"name":"Nerissa T. Williams","orcid":"0000-0003-0554-9222","position":3,"is_corresponding":false},{"id":491683,"name":"Yan Ma","orcid":"0000-0002-1649-8849","position":4,"is_corresponding":false},{"id":926839,"name":"Joshua A. Regal","orcid":"0000-0001-5142-0978","position":5,"is_corresponding":false},{"id":927297,"name":"Debosir Ghosh","orcid":null,"position":6,"is_corresponding":false},{"id":926840,"name":"Patrick Sansone","orcid":"0000-0001-8060-6026","position":7,"is_corresponding":false},{"id":873699,"name":"Mark Oldham","orcid":"0000-0002-0981-7522","position":8,"is_corresponding":false},{"id":824904,"name":"Katherine Deland","orcid":"0009-0008-0739-7529","position":9,"is_corresponding":false},{"id":305860,"name":"Oren J. Becher","orcid":"0000-0003-4016-8492","position":10,"is_corresponding":false},{"id":334422,"name":"David G. Kirsch","orcid":"0000-0002-2086-205X","position":11,"is_corresponding":false},{"id":1400,"name":"Zachary J. Reitman","orcid":"0000-0002-9122-9550","position":12,"is_corresponding":false},{"id":926838,"name":"Connor E. Stewart","orcid":"0000-0003-1115-2272","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:26:58.102271Z","pmid":"36139666","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":[]}