{"doi":"10.1111/cas.14597","title":"A tailored next‐generation sequencing panel identified distinct subtypes of wildtype IDH and TERT promoter glioblastomas","abstract":"<jats:title>Abstract</jats:title><jats:p>Central nervous system tumors are classified based on an integrated diagnosis combining histology and molecular characteristics, including <jats:italic>IDH1/2</jats:italic> and <jats:italic>H3</jats:italic>‐K27M mutations, as well as 1p/19q codeletion. Here, we aimed to develop and assess the feasibility of a glioma‐tailored 48‐gene next‐generation sequencing (NGS) panel for integrated glioma diagnosis. We designed a glioma‐tailored 48‐gene NGS panel for detecting 1p/19q codeletion and mutations in <jats:italic>IDH1/2</jats:italic>, <jats:italic>TP53</jats:italic>, <jats:italic>PTEN</jats:italic>, <jats:italic>PDGFRA</jats:italic>, <jats:italic>NF1</jats:italic>, <jats:italic>RB1</jats:italic>, <jats:italic>CDKN2A/B</jats:italic>, <jats:italic>CDK4</jats:italic>, and the <jats:italic>TERT</jats:italic> promoter (<jats:italic>TERTp</jats:italic>). We analyzed 106 glioma patients (grade II: 19 cases, grade III: 23 cases, grade IV: 64 cases) using this system. The 1p/19q codeletion was detected precisely in oligodendroglial tumors using our NGS panel. In a cohort of 64 grade Ⅳ gliomas, we identified 56 <jats:italic>IDH</jats:italic>‐wildtype glioblastomas. Within these <jats:italic>IDH</jats:italic>‐wildtype glioblastomas, 33 samples (58.9%) showed a mutation in <jats:italic>TERTp</jats:italic>. Notably, <jats:italic>PDGFRA</jats:italic> mutations and their amplification were more commonly seen in <jats:italic>TERTp</jats:italic>‐wildtype glioblastomas (43%) than in <jats:italic>TERTp</jats:italic>‐mutant glioblastomas (6%) (<jats:italic>P</jats:italic> = .001). Hierarchical molecular classification of <jats:italic>IDH</jats:italic>‐wildtype glioblastomas revealed 3 distinct groups of <jats:italic>IDH</jats:italic>‐wildtype glioblastomas. One major cluster was characterized by mutations in <jats:italic>PDGFRA</jats:italic>, amplification of <jats:italic>CDK4</jats:italic> and <jats:italic>PDGFRA</jats:italic>, homozygous deletion of <jats:italic>CDKN2A/B</jats:italic>, and absence of <jats:italic>TERTp</jats:italic> mutations. This cluster was significantly associated with older age (<jats:italic>P</jats:italic> = .021), higher Ki‐67 score (<jats:italic>P</jats:italic> = .007), poor prognosis (<jats:italic>P</jats:italic> = .012), and a periventricular tumor location. We report the development of a glioma‐tailored NGS panel for detecting 1p/19q codeletion and driver gene mutations on a single platform. Our panel identified distinct subtypes of <jats:italic>IDH</jats:italic>‐ and <jats:italic>TERTp</jats:italic>‐wildtype glioblastomas with frequent <jats:italic>PDGFRA</jats:italic> alterations.</jats:p>","journal":"Cancer Science","year":2020,"id":634797,"datarank":0.5983476069846413,"base_score":3.9889840465642745,"endowment":3.9889840465642745,"self_citation_contribution":0.5983476069846413,"citation_network_contribution":0.0,"self_endowment_contribution":0.5983476069846413,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":53,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1646582,"name":"Toshiaki Akahane","orcid":null,"position":1,"is_corresponding":false},{"id":1646583,"name":"Seiya Yokoyama","orcid":null,"position":2,"is_corresponding":false},{"id":1646585,"name":"Hajime Yonezawa","orcid":null,"position":3,"is_corresponding":false},{"id":487337,"name":"Hiroyuki Uchida","orcid":"0000-0002-0628-7036","position":4,"is_corresponding":false},{"id":1646589,"name":"Tomoko Takajo","orcid":null,"position":5,"is_corresponding":false},{"id":1646591,"name":"Mari Kirishima","orcid":null,"position":6,"is_corresponding":false},{"id":1646593,"name":"Taiji Hamada","orcid":null,"position":7,"is_corresponding":false},{"id":1646595,"name":"Kei Matsuo","orcid":null,"position":8,"is_corresponding":false},{"id":400275,"name":"Shingo Fujio","orcid":"0000-0001-8813-5038","position":9,"is_corresponding":false},{"id":1646600,"name":"Tomoko Hanada","orcid":null,"position":10,"is_corresponding":false},{"id":1646603,"name":"Hiroshi Hosoyama","orcid":null,"position":11,"is_corresponding":false},{"id":1646606,"name":"Masanori Yonenaga","orcid":null,"position":12,"is_corresponding":false},{"id":1646610,"name":"Akihisa Sakamoto","orcid":null,"position":13,"is_corresponding":false},{"id":1646614,"name":"Tsubasa Hiraki","orcid":null,"position":14,"is_corresponding":false},{"id":1646619,"name":"Akihide Tanimoto","orcid":"0000-0001-7508-1624","position":15,"is_corresponding":false},{"id":400276,"name":"Koji Yoshimoto","orcid":"0000-0001-7912-2024","position":16,"is_corresponding":false},{"id":1646581,"name":"Nayuta Higa","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A tailored next‐generation sequencing panel identified distinct subtypes of wildtype IDH and TERT promoter glioblastomas","abstract":"<jats:title>Abstract</jats:title><jats:p>Central nervous system tumors are classified based on an integrated diagnosis combining histology and molecular characteristics, including <jats:italic>IDH1/2</jats:italic> and <jats:italic>H3</jats:italic>‐K27M mutations, as well as 1p/19q codeletion. Here, we aimed to develop and assess the feasibility of a glioma‐tailored 48‐gene next‐generation sequencing (NGS) panel for integrated glioma diagnosis. We designed a glioma‐tailored 48‐gene NGS panel for detecting 1p/19q codeletion and mutations in <jats:italic>IDH1/2</jats:italic>, <jats:italic>TP53</jats:italic>, <jats:italic>PTEN</jats:italic>, <jats:italic>PDGFRA</jats:italic>, <jats:italic>NF1</jats:italic>, <jats:italic>RB1</jats:italic>, <jats:italic>CDKN2A/B</jats:italic>, <jats:italic>CDK4</jats:italic>, and the <jats:italic>TERT</jats:italic> promoter (<jats:italic>TERTp</jats:italic>). We analyzed 106 glioma patients (grade II: 19 cases, grade III: 23 cases, grade IV: 64 cases) using this system. The 1p/19q codeletion was detected precisely in oligodendroglial tumors using our NGS panel. In a cohort of 64 grade Ⅳ gliomas, we identified 56 <jats:italic>IDH</jats:italic>‐wildtype glioblastomas. Within these <jats:italic>IDH</jats:italic>‐wildtype glioblastomas, 33 samples (58.9%) showed a mutation in <jats:italic>TERTp</jats:italic>. Notably, <jats:italic>PDGFRA</jats:italic> mutations and their amplification were more commonly seen in <jats:italic>TERTp</jats:italic>‐wildtype glioblastomas (43%) than in <jats:italic>TERTp</jats:italic>‐mutant glioblastomas (6%) (<jats:italic>P</jats:italic> = .001). Hierarchical molecular classification of <jats:italic>IDH</jats:italic>‐wildtype glioblastomas revealed 3 distinct groups of <jats:italic>IDH</jats:italic>‐wildtype glioblastomas. One major cluster was characterized by mutations in <jats:italic>PDGFRA</jats:italic>, amplification of <jats:italic>CDK4</jats:italic> and <jats:italic>PDGFRA</jats:italic>, homozygous deletion of <jats:italic>CDKN2A/B</jats:italic>, and absence of <jats:italic>TERTp</jats:italic> mutations. This cluster was significantly associated with older age (<jats:italic>P</jats:italic> = .021), higher Ki‐67 score (<jats:italic>P</jats:italic> = .007), poor prognosis (<jats:italic>P</jats:italic> = .012), and a periventricular tumor location. We report the development of a glioma‐tailored NGS panel for detecting 1p/19q codeletion and driver gene mutations on a single platform. Our panel identified distinct subtypes of <jats:italic>IDH</jats:italic>‐ and <jats:italic>TERTp</jats:italic>‐wildtype glioblastomas with frequent <jats:italic>PDGFRA</jats:italic> alterations.</jats:p>","is_dataset_classified":null,"base_score":3.9889840465642745,"endowment":3.9889840465642745,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"32748499","pmcid":"PMC7541004","openalex_id":"https://openalex.org/W3047211934","authors":[],"funders":[],"total_grants":0,"fwci":3.5948,"citation_percentile":0.9407953,"influential_citations":0,"citation_trend":[{"year":2021,"count":2},{"year":2022,"count":18},{"year":2023,"count":12},{"year":2024,"count":8},{"year":2025,"count":9},{"year":2026,"count":4}],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://doi.org/10.1111/cas.14597","host_type":"journal"},{"url":"https://doi.org/10.1111/cas.14597","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fcas.14597","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/cas.14597","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cas.14597","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/32748499","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7541004","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC7541004","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7541004?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Glioma Diagnosis and Treatment","Cancer Genomics and Diagnostics","Chromatin Remodeling and Cancer"],"mesh_terms":["Adult","Aged","Aged, 80 and over","Female","Glioblastoma","Humans","Isocitrate Dehydrogenase","Male","Middle Aged","Neoplasm Proteins","Promoter Regions, Genetic","Telomerase","Receptor, Platelet-Derived Growth Factor alpha","High-Throughput Nucleotide Sequencing"],"keywords":["PDGFRA","CDKN2A","IDH1","Glioma","Wild type","Cancer research","PTEN","Biology","Oligodendroglioma","Oligodendroglial Tumor","Pathology","Medicine","Mutation","Gene","Mutant","Genetics","Astrocytoma","PI3K/AKT/mTOR pathway","Stromal cell","Apoptosis","Glioblastoma","Next-generation Sequencing","1P/19q Codeletion","Tert Promoter","Pdgfra Alterations"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"No poverty"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T14:11:20.697478Z","pmid":null,"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":[]}