Clinical and molecular heterogeneity of pineal parenchymal tumors: a consensus study
| Autor: | Christelle Dufour, Annie Huang, Nancy Bouvier, Cynthia Hawkins, Brian Gudenas, Eric Bouffet, Matthias A. Karajannis, Marcel Kool, Alexandru Szathmari, Cécile Faure-Conter, Amar Gajjar, Stefan Rutkowski, Brent A. Orr, Jordan R. Hansford, Stefan M. Pfister, Anthony P. Y. Liu, Arzu Onar-Thomas, Eugene Hwang, Martin Mynarek, Ho Keung Ng, Elke Pfaff, Felix Sahm, Thomas E. Merchant, Alexandre Vasiljevic, Giles W. Robinson, Paul A. Northcott, Katja von Hoff, Bryan K. Li, David T.W. Jones, Matija Snuderl, Max Levine, Marc K. Rosenblum |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology medicine.medical_specialty Adolescent Age at diagnosis Disease Bioinformatics Pineal Gland Molecular heterogeneity Article Pathology and Forensic Medicine Cohort Studies Transcriptome Intermediate differentiation Young Adult 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Internal medicine Humans Medicine Child Pineoblastoma Brain Neoplasms business.industry Infant Newborn Infant DNA Methylation Middle Aged Diagnostic classification Clinical trial 030104 developmental biology Pineal Parenchymal Tumors Child Preschool DNA methylation Female Neurology (clinical) business Pinealoma MicroRNA processing 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Acta Neuropathol |
| ISSN: | 1432-0533 0001-6322 |
| DOI: | 10.1007/s00401-021-02284-5 |
| Popis: | BackgroundRecent genomic studies have shed light on the biology and inter-tumoral heterogeneity underlying pineal parenchymal tumors, in particular pineoblastomas (PBs) and pineal parenchymal tumors of intermediate differentiation (PPTIDs). Previous reports, however, had modest sample sizes and lacked power to integrate molecular and clinical findings. The different proposed subgroup structures also highlighted a need to reach consensus on a robust and relevant classification system.MethodsWe performed a meta-analysis on 221 patients with molecularly characterized PBs and PPTIDs. DNA methylation profiles were analyzed through complementary bioinformatic approaches and molecular subgrouping was harmonized. Demographic, clinical and genomic features of patients and samples from these pineal tumor subgroups were annotated.FindingsFour clinically and biologically relevant consensus PB subgroups were defined: PB-miRNA1 (n=96), PB-miRNA2 (n=23), PB-MYC/FOXR2 (n=34) and PB-RB1 (n=25); with PPTID (n=43) remaining as a molecularly distinct entity. Genomic and transcriptomic profiling allowed the characterization of oncogenic drivers for individual subgroups, specifically, alterations in the microRNA processing pathway in PB-miRNA1/2, MYC amplification and FOXR2 overexpression in PB-MYC/FOXR2, RB1 alteration in PB-RB1, and KBTBD4 insertion in PPTID. Age at diagnosis, sex predilection and metastatic status varied significantly among tumor subgroups. While patients with PB-miRNA2 and PPTID had superior outcome, survival was intermediate for patients with PB-miRNA1, and dismal for those with PB-MYC/FOXR2 and PB-RB1.InterpretationWe systematically interrogated the clinical and molecular heterogeneity within pineal parenchymal tumors and proposed a consensus nomenclature for disease subgroups, laying the groundwork for future studies as well as routine use in tumor classification. |
| Databáze: | OpenAIRE |
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