Molecular alterations in pediatric brainstem gliomas

Show simple item record Porkholm, Mikaela Raunio, Anna Vainionpää, Reetta Salonen, Tarja Hernesniemi, Juha Valanne, Leena Satopää, Jarno Karppinen, Atte Oinas, Minna Tynninen, Olli Kivivuori, Sanna-Maria 2019-05-31T21:40:38Z 2021-12-17T22:02:46Z 2018-01
dc.identifier.citation Porkholm , M , Raunio , A , Vainionpää , R , Salonen , T , Hernesniemi , J , Valanne , L , Satopää , J , Karppinen , A , Oinas , M , Tynninen , O & Kivivuori , S-M 2018 , ' Molecular alterations in pediatric brainstem gliomas ' , Pediatric Blood & Cancer , vol. 65 , no. 1 , 26751 .
dc.identifier.other PURE: 97522119
dc.identifier.other PURE UUID: 73a1d159-a354-4bf7-b2b6-1a3f4e250cee
dc.identifier.other Scopus: 85035027962
dc.identifier.other WOS: 000416119400040
dc.identifier.other ORCID: /0000-0003-0356-7048/work/46037614
dc.identifier.other ORCID: /0000-0002-2674-0301/work/57547795
dc.identifier.other ORCID: /0000-0002-6150-091X/work/58033179
dc.identifier.other ORCID: /0000-0003-0788-3662/work/60612545
dc.description.abstract BackgroundDiffuse intrinsic pontine gliomas (DIPGs) have a dismal prognosis. Previously, diagnosis was based on a typical clinical presentation and magnetic resonance imaging findings. After the start of the era of biopsies, DIPGs bearing H3 K27 mutations have been reclassified into a novel entity, diffuse midline glioma, based on the presence of this molecular alteration. However, it is not well established how clinically diagnosed DIPG overlap with H3 K27-mutated diffuse midline gliomas, and whether rare long-term survivors also belong to this group. MethodsWe studied tumor samples obtained at diagnosis or upon autopsy from 23 children, including two long-term survivors. Based on clinical, radiological, and histological findings, all tumors were previously diagnosed as DIPGs. All samples were analyzed for genetic alterations by next-generation sequencing (NGS) and for protein expression by immunohistochemistry (IHC). ResultsH3 K27 was mutated in NGS or IHC in 20 patients, excluding both long-term survivors. One of these long-term survivors harbored a mutation in IDH1, formerly considered to be an alteration absent in pediatric diffuse brainstem gliomas. Other altered genes in NGS included TP53 (10 patients), MET and PDGFRA (3 patients each), VEGFR and SMARCA4 (2 patients each), and PPAR, PTEN and EGFR in 1 patient, respectively. IHC revealed cMYC expression in 15 of 24 (63%) of all samples, exclusively in the biopsies. ConclusionsEighty-seven percent of the tumors formerly diagnosed as DIPGs could be reclassified as H3 K27-mutated diffuse midline gliomas. Both long-term survivors lacked this alteration. Contrary to former conceptions, IDH1 mutations may occur also in pediatric brainstem gliomas. en
dc.format.extent 8
dc.language.iso eng
dc.relation.ispartof Pediatric Blood & Cancer
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject 3122 Cancers
dc.subject 3123 Gynaecology and paediatrics
dc.title Molecular alterations in pediatric brainstem gliomas en
dc.type Article
dc.contributor.organization Clinicum
dc.contributor.organization Children's Hospital
dc.contributor.organization University of Helsinki
dc.contributor.organization HUS Children and Adolescents
dc.contributor.organization HUSLAB
dc.contributor.organization Medicum
dc.contributor.organization Department of Pathology
dc.contributor.organization Department of Medical and Clinical Genetics
dc.contributor.organization Neurokirurgian yksikkö
dc.contributor.organization HUS Neurocenter
dc.contributor.organization Department of Diagnostics and Therapeutics
dc.contributor.organization HUS Medical Imaging Center
dc.description.reviewstatus Peer reviewed
dc.relation.issn 1545-5009
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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