{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T06:18:08Z","timestamp":1768717088522,"version":"3.49.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019714","name":"Foundation Medicine Inc","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019714","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The authors present a cohort of 661 young adult glioblastomas diagnosed using 2016 WHO World Health Organization Classification of Tumors of the Central Nervous System, utilizing comprehensive genomic profiling (CGP) to explore their genomic landscape and assess their relationship to currently defined disease entities. This analysis explored variants with evidence of pathogenic function, common copy number variants (CNVs), and several novel fusion events not described in literature. Tumor mutational burden (TMB) mutational signatures, anatomic location, and tumor recurrence are further explored. Using data collected from CGP, unsupervised machine-learning techniques were leveraged to identify 10 genomic classes in previously assigned young adult glioblastomas. The authors relate these molecular classes to current World Health Organization guidelines and reference current literature to give therapeutic and prognostic descriptions where possible.<\/jats:p>","DOI":"10.1093\/oncolo\/oyad224","type":"journal-article","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T00:15:39Z","timestamp":1692922539000},"page":"e47-e58","source":"Crossref","is-referenced-by-count":5,"title":["A Retrospective Genomic Landscape of 661 Young Adult Glioblastomas Diagnosed Using 2016 WHO Guidelines for Central Nervous System Tumors"],"prefix":"10.1093","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3411-0318","authenticated-orcid":false,"given":"James F","family":"Haberberger","sequence":"first","affiliation":[{"name":"Pathology Department, Foundation Medicine , Morrisville, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Worthy","family":"Pegram","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Morrisville, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Britt","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Morrisville, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelsie","family":"Schiavone","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Morrisville, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Severson","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Morrisville, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5214-380X","authenticated-orcid":false,"given":"Radwa","family":"Sharaf","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Cambridge, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee A","family":"Albacker","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Cambridge, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Williams","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Cambridge, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirna","family":"Lechpammer","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Morrisville, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Hemmerich","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Morrisville, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas","family":"Lin","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Morrisville, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard S P","family":"Huang","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Morrisville, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Hiemenz","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Cambridge, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Elvin","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Cambridge, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryon","family":"Graf","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Cambridge, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn","family":"Lesser","sequence":"additional","affiliation":[{"name":"Pathology Department, Section on Hematology-Oncology, Wake Forest School of Medicine , Winston Salem, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Kram","sequence":"additional","affiliation":[{"name":"Pathology Department, Section on Hematology-Oncology, Wake Forest School of Medicine , Winston Salem, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roy","family":"Strowd","sequence":"additional","affiliation":[{"name":"Pathology Department, Section on Hematology-Oncology, Wake Forest School of Medicine , Winston Salem, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4635-0247","authenticated-orcid":false,"given":"Wenya Linda","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital , Boston, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lori A","family":"Ramkissoon","sequence":"additional","affiliation":[{"name":"Pathology Department, University of North Carolina School of Medicine , Chapel Hill, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael B","family":"Cohen","sequence":"additional","affiliation":[{"name":"Wake Forest Comprehensive Cancer Center and Department of Pathology, Wake Forest School of Medicine , Winston-Salem, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prasanth","family":"Reddy","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Cambridge, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Creeden","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Cambridge, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey S","family":"Ross","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Cambridge, MA , USA"},{"name":"Pathology Department, SUNY Upstate Medical University , Syracuse, NY , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian M","family":"Alexander","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Cambridge, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shakti H","family":"Ramkissoon","sequence":"additional","affiliation":[{"name":"Pathology Department, Foundation Medicine , Morrisville, NC , USA"},{"name":"Wake Forest Comprehensive Cancer Center and Department of Pathology, Wake Forest School of Medicine , Winston-Salem, NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,8,24]]},"reference":[{"key":"2024010523370187900_CIT0001","first-page":"4085","article-title":"Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial","volume-title":"J Clin Oncol","author":"Gilbert","year":"2013"},{"key":"2024010523370187900_CIT0002","first-page":"2048","article-title":"Bevacizumab for newly diagnosed glioblastoma","volume-title":"N Engl J Med","author":"Gilbert","year":"2014"},{"key":"2024010523370187900_CIT0003","first-page":"vdaa009","article-title":"Targeted next-generation sequencing of 565 neuro-oncology patients at UCLA: a single-institution experience","volume-title":"Neurooncol Adv","author":"Ji","year":"2020"},{"key":"2024010523370187900_CIT0004","first-page":"1231","article-title":"The 2021 WHO classification of tumors of the central nervous system: a summary","volume-title":"Neuro Oncol","author":"Louis","year":"2021"},{"key":"2024010523370187900_CIT0005","first-page":"301","article-title":"The 2016 WHO classification of tumours of the central nervous system: the major points of revision","volume-title":"Neurol Med Chir (Tokyo)","author":"Komori","year":"2017"},{"key":"2024010523370187900_CIT0006","first-page":"8083","article-title":"Clinical multiplexed exome sequencing distinguishes adult oligodendroglial neoplasms from astrocytic and mixed lineage gliomas","volume-title":"Oncotarget","author":"Cryan","year":"2014"},{"key":"2024010523370187900_CIT0007","first-page":"903","article-title":"Next-generation sequencing in routine brain tumor diagnostics enables an integrated diagnosis and identifies actionable targets","volume-title":"Acta Neuropathol","author":"Sahm","year":"2016"},{"issue":"26","key":"2024010523370187900_CIT0008","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1056\/NEJMoa1402121","article-title":"Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas","volume":"372","author":"TCGA","year":"2015","journal-title":"N Engl J Med"},{"key":"2024010523370187900_CIT0009","first-page":"1478","article-title":"Comprehensive genomic profiling of 282 pediatric low- and high-grade gliomas reveals genomic drivers, tumor mutational burden, and hypermutation signatures","volume-title":"Oncologist","author":"Johnson","year":"2017"},{"key":"2024010523370187900_CIT0010","first-page":"136","article-title":", Glioblastomas harboring gene fusions detected by next-generation sequencing","volume-title":"Brain Tumor Pathol","author":"Woo","year":"2020"},{"key":"2024010523370187900_CIT0011","first-page":"1344","article-title":"Clinical implementation of integrated whole-genome copy number and mutation profiling for glioblastoma","volume-title":"Neuro Oncol","author":"Ramkissoon","year":"2015"},{"key":"2024010523370187900_CIT0012","first-page":"618","article-title":"Whole genome sequence analysis links chromothripsis to EGFR, MDM2, MDM4, and CDK4 amplification in glioblastoma","volume-title":"Oncoscience","author":"Furgason","year":"2015"},{"key":"2024010523370187900_CIT0013","first-page":"774","article-title":"Mutant IDH1 regulates the tumor-associated immune system in gliomas","volume-title":"Genes Dev","author":"Amankulor","year":"2017"},{"key":"2024010523370187900_CIT0014","first-page":"2386","article-title":"Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML","volume-title":"N Engl J Med","author":"DiNardo","year":"2018"},{"key":"2024010523370187900_CIT0015","first-page":"417","article-title":"Mutant isocitrate dehydrogenase inhibitors as targeted cancer therapeutics","volume-title":"Front Oncol","author":"Golub","year":"2019"},{"key":"2024010523370187900_CIT0016","volume-title":"FoundationOne CDx Technical Information","author":"Inc, F.M"},{"key":"2024010523370187900_CIT0017","first-page":"703","article-title":"Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients","volume-title":"Nat Med","author":"Zehir","year":"2017"},{"issue":"2","key":"2024010523370187900_CIT0018","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/BF02294508","article-title":"The EM algorithm for latent class analysis with equality constraints","volume":"57","author":"Van Der Heijden","year":"1992","journal-title":"Psychometrika"},{"issue":"26","key":"2024010523370187900_CIT0019","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1056\/NEJMoa1402121","article-title":"Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas","volume":"372","author":"Cancer Genome Atlas Research, N","year":"2015","journal-title":"N Engl J Med"},{"key":"2024010523370187900_CIT0020","first-page":"vdab017","article-title":"FoundationOne CDx testing accurately determines whole arm 1p19q codeletion status in gliomas","volume-title":"Neurooncol Adv","author":"Sharaf","year":"2021"},{"key":"2024010523370187900_CIT0021","first-page":"1267","article-title":"Low-grade astrocytoma mutations in IDH1, P53, and ATRX cooperate to block differentiation of human neural stem cells via repression of SOX2","volume-title":"Cell Rep","author":"Modrek","year":"2017"},{"key":"2024010523370187900_CIT0022","first-page":"76","article-title":"Downregulation of CDKN2A and suppression of cyclin D1 gene expressions in malignant gliomas","volume-title":"J Exp Clin Cancer Res.","author":"Liu","year":"2011"},{"issue":"11","key":"2024010523370187900_CIT0023","first-page":"4151","article-title":"Short postoperative survival for glioblastoma patients with a dysfunctional Rb1 pathway in combination with no wild-type PTEN","volume":"9","author":"Backlund","year":"2003","journal-title":"Clin Cancer Res"},{"key":"2024010523370187900_CIT0024","first-page":"1519","article-title":"CDKN2A homozygous deletion is a strong adverse prognosis factor in diffuse malignant IDH-mutant gliomas","volume-title":"Neuro-Oncology","author":"Appay","year":"2019"},{"key":"2024010523370187900_CIT0025","first-page":"590","article-title":"Loss of CDKN2A expression is a frequent event in primary invasive melanoma and correlates with sensitivity to the CDK4\/6 inhibitor PD0332991 in melanoma cell lines","volume-title":"Pigment Cell Melanoma Res.","author":"Young","year":"2014"},{"key":"2024010523370187900_CIT0026","first-page":"e498","article-title":"Does CDKN2A loss predict palbociclib benefit?","volume-title":"Curr Oncol","author":"Gao","year":"2015"},{"key":"2024010523370187900_CIT0027","first-page":"1345","article-title":"Telomerase reverse transcriptase induced thyroid carcinoma cell proliferation through PTEN\/AKT signaling pathway","volume-title":"Mol Med Rep","author":"Zhang","year":"2018"},{"key":"2024010523370187900_CIT0028","first-page":"8213","article-title":"Preclinical and clinical implications of TERT promoter mutation in glioblastoma multiforme","volume-title":"Oncol Lett","author":"Jeong","year":"2017"},{"key":"2024010523370187900_CIT0029","first-page":"2247","article-title":"Eribulin penetrates brain tumor tissue and prolongs survival of mice harboring intracerebral glioblastoma xenografts","volume-title":"Cancer Sci","author":"Takahashi","year":"2019"},{"key":"2024010523370187900_CIT0030","first-page":"425","article-title":"Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma","volume-title":"Cancer Cell.","author":"Sturm","year":"2012"},{"key":"2024010523370187900_CIT0031","first-page":"59098","article-title":"Co-expression modules of NF1, PTEN and sprouty enable distinction of adult diffuse gliomas according to pathway activities of receptor tyrosine kinases","volume-title":"Oncotarget","author":"Zhang","year":"2016"},{"key":"2024010523370187900_CIT0032","first-page":"125","article-title":"Applied cancer immunogenomics: leveraging neoantigen discovery in glioblastoma","volume-title":"Cancer J","author":"Johanns","year":"2017"},{"key":"2024010523370187900_CIT0033","first-page":"319","article-title":"Pediatric high grade gliomas in the context of cancer predisposition syndromes","volume-title":"J Korean Neurosurg Soc","author":"Michaeli","year":"2018"},{"key":"2024010523370187900_CIT0034","first-page":"517","article-title":"Mechanisms and therapeutic implications of hypermutation in gliomas","volume-title":"Nature","author":"Touat","year":"2020"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/29\/1\/e47\/55119162\/oyad224.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/29\/1\/e47\/55119162\/oyad224.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T23:38:00Z","timestamp":1704497880000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/29\/1\/e47\/7250313"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,24]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,8,24]]},"published-print":{"date-parts":[[2024,1,5]]}},"URL":"https:\/\/doi.org\/10.1093\/oncolo\/oyad224","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,1,1]]},"published":{"date-parts":[[2023,8,24]]}}}