Molecular alterations in pediatric brainstem gliomas
| Autor: | Leena Valanne, Reetta Vainionpää, Virve Pentikäinen, Sanna-Maria Kivivuori, Atte Karppinen, Jarno Satopää, Anna Raunio, Minna Oinas, Juha Hernesniemi, Olli Tynninen, Mikaela Porkholm, Tarja Salonen |
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| Přispěvatelé: | Clinicum, Children's Hospital, University of Helsinki, HUS Children and Adolescents, HUSLAB, Medicum, Department of Pathology, Department of Medical and Clinical Genetics, Neurokirurgian yksikkö, HUS Neurocenter, Department of Diagnostics and Therapeutics, HUS Medical Imaging Center |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Pathology medicine.medical_specialty IDH1 Adolescent Biopsy 3122 Cancers Autopsy Nerve Tissue Proteins PDGFRA 03 medical and health sciences 3123 Gynaecology and paediatrics Glioma Brainstem glioma medicine PTEN Brain Stem Neoplasms Humans Child medicine.diagnostic_test biology business.industry High-Throughput Nucleotide Sequencing Magnetic resonance imaging Hematology medicine.disease 3. Good health Neoplasm Proteins Gene Expression Regulation Neoplastic 030104 developmental biology Oncology Child Preschool Pediatrics Perinatology and Child Health biology.protein Immunohistochemistry Female business |
| Zdroj: | Pediatric bloodcancer. 65(1) |
| ISSN: | 1545-5017 |
| Popis: | Background Diffuse 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. Methods We 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). Results H3 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 PPARγ, PTEN and EGFR in 1 patient, respectively. IHC revealed cMYC expression in 15 of 24 (63%) of all samples, exclusively in the biopsies. Conclusions Eighty-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. |
| Databáze: | OpenAIRE |
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