Molecular Alterations in Pediatric Low-Grade Gliomas That Led to Death
- 27 September 2021
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Neuropathology and Experimental Neurology
- Vol. 80 (11), 1052-1059
- https://doi.org/10.1093/jnen/nlab097
Abstract
Pediatric low-grade gliomas (PLGGs) have excellent long-term survival, but death can occasionally occur. We reviewed all PLGG-related deaths between 1975 and 2019 at our institution: 48 patients were identified; clinical data and histology were reviewed; targeted exome sequencing was performed on available material. The median age at diagnosis was 5.2 years (0.4–23.4 years), at death was 13.0 years (1.9–43.2 years), and the overall survival was 7.2 years (0.0–33.3 years). Tumors were located throughout CNS, but predominantly in the diencephalon. Diagnoses included low-grade glioma, not otherwise specified (n = 25), pilocytic astrocytoma (n = 15), diffuse astrocytoma (n = 3), ganglioglioma (n = 3), and pilomyxoid astrocytoma (n = 2). Recurrence occurred in 42/48 cases, whereas progression occurred in 10. The cause of death was direct tumor involvement in 31/48 cases. Recurrent drivers included KIAA1549-BRAF (n = 13), BRAF(V600E) (n = 3), NF1 mutation (n = 3), EGFR mutation (n = 3), and FGFR1-TACC1 fusion (n = 2). Single cases were identified with IDH1(R132H), FGFR1(K656E), FGFR1 ITD, FGFR3 gain, PDGFRA amplification, and mismatch repair alteration. CDKN2A/B, CDKN2C, and PTEN loss was recurrent. Patients who received only chemotherapy had worse survival compared with patients who received radiation and chemotherapy. This study demonstrates that PLGG that led to death have diverse molecular characteristics. Location and co-occurring molecular alterations with malignant potential can predict poor outcomes.Keywords
This publication has 36 references indexed in Scilit:
- The Somatic Genomic Landscape of GlioblastomaCell, 2013
- Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytomaNature Genetics, 2013
- Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomasNature Genetics, 2013
- Hotspot Mutations in H3F3A and IDH1 Define Distinct Epigenetic and Biological Subgroups of GlioblastomaCancer Cell, 2012
- Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastomaNature, 2012
- Bereaved Parents' Perceptions of the Autopsy Examination of Their ChildPEDIATRICS, 2011
- Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1Cancer Cell, 2010
- Spontaneous Regression of Low-Grade Gliomas in Pediatric Patients without NeurofibromatosisPediatric Neurosurgery, 2008
- Clinical and Molecular Characteristics of Malignant Transformation of Low-Grade Glioma in ChildrenJournal of Clinical Oncology, 2007
- Spontaneous regression of residual low-grade cerebellar pilocytic astrocytomas in childrenPediatric Radiology, 2005