Molecular alterations in pediatric brainstem gliomas

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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 .

Julkaisun nimi: Molecular alterations in pediatric brainstem gliomas
Tekijä: Porkholm, Mikaela; Raunio, Anna; Vainionpää, Reetta; Salonen, Tarja; Hernesniemi, Juha; Valanne, Leena; Satopää, Jarno; Karppinen, Atte; Oinas, Minna; Tynninen, Olli; Kivivuori, Sanna-Maria
Tekijän organisaatio: Clinicum
Children's Hospital
University of Helsinki
HUS Children and Adolescents
Department of Pathology
Department of Medical and Clinical Genetics
Neurokirurgian yksikkö
HUS Neurocenter
Department of Diagnostics and Therapeutics
HUS Medical Imaging Center
Päiväys: 2018-01
Kieli: eng
Sivumäärä: 8
Kuuluu julkaisusarjaan: Pediatric Blood & Cancer
ISSN: 1545-5009
Tiivistelmä: 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.
Avainsanat: 3122 Cancers
3123 Gynaecology and paediatrics
Vertaisarvioitu: Kyllä
Pääsyrajoitteet: openAccess
Rinnakkaistallennettu versio: publishedVersion


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