{"doi":"10.1093/noajnl/vdab050","title":"The role of <i>RB1</i> alteration and 4q12 amplification in IDH-WT glioblastoma","abstract":"Abstract Background Recent studies have identified that glioblastoma IDH-wildtype (GBM IDH-WT) might be comprised of molecular subgroups with distinct prognoses. Therefore, we investigated the correlation between genetic alterations and survival in 282 GBM IDH-WT patients, to identify subgroups with distinct outcomes. Methods We reviewed characteristics of GBM IDH-WT (2009–2019) patients analyzed by next-generation sequencing interrogating 205 genes and 26 rearrangements. Progression-free survival (PFS) and overall survival (OS) were evaluated with the log-rank test and Cox regression models. We validated our results utilizing data from cBioPortal (MSK-IMPACT dataset). Results Multivariable analysis of GBM IDH-WT revealed that treatment with chemoradiation and RB1-mutant status correlated with improved PFS (hazard ratio [HR] 0.25, P &amp;lt; .001 and HR 0.47, P = .002) and OS (HR 0.24, P &amp;lt; .001 and HR 0.49, P = .016). In addition, younger age (&amp;lt;55 years) was associated with improved OS. Karnofsky performance status less than 80 (HR 1.44, P = .024) and KDR amplification (HR 2.51, P = .008) were predictors of worse OS. KDR-amplified patients harbored coexisting PDGFRA and KIT amplification (P &amp;lt; .001) and TP53 mutations (P = .04). RB1-mutant patients had less frequent CDKN2A/B and EGFR alterations (P &amp;lt; .001). Conversely, RB1-mutant patients had more frequent TP53 (P &amp;lt; .001) and SETD2 (P = .006) mutations. Analysis of the MSK-IMPACT dataset (n = 551) validated the association between RB1 mutations and improved PFS (11.0 vs 8.7 months, P = .009) and OS (34.7 vs 21.7 months, P = .016). Conclusions RB1-mutant GBM IDH-WT is a molecular subgroup with improved PFS and OS. Meanwhile, 4q12 amplification (KDR/PDGFRA/KIT) denoted patients with worse OS. Identifying subgroups of GBM IDH-WT with distinct survival is important for optimal clinical trial design, incorporation of targeted therapies, and personalized neuro-oncological care.","journal":"Neuro-Oncology Advances","year":2021,"id":176240,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9097,"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":718267,"name":"Arvind V. Ramesh","orcid":"0009-0005-2977-5787","position":1,"is_corresponding":false},{"id":718766,"name":"Emily Wang","orcid":null,"position":2,"is_corresponding":false},{"id":489118,"name":"Mauli Shah","orcid":"0000-0002-1131-9338","position":3,"is_corresponding":false},{"id":277125,"name":"Nitin Tandon","orcid":"0000-0002-2752-2365","position":4,"is_corresponding":false},{"id":277127,"name":"Leomar Y. Ballester","orcid":"0000-0002-6854-6830","position":5,"is_corresponding":false},{"id":277128,"name":"Yoshua Esquenazi","orcid":"0000-0002-9757-1453","position":6,"is_corresponding":false},{"id":277119,"name":"Antonio Dono","orcid":"0000-0002-8041-8399","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T23:47:19.591542Z","pmid":"34131647","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":[]}