SINGLE INSTITUTION EXPERIENCE USING MOLECULAR ANALYSIS OF PEDIATRIC CNS TUMORS
Neuro-Oncology(2022)
摘要
Abstract Molecular analysis of pediatric CNS tumors helps confirm the diagnosis, but can also guide treatment by identifying prognostic factors allowing for treatment stratification, and by unveiling active signaling pathways which can be targeted. This report is a retrospective review of the molecular analysis performed on all CNS tumors biopsied or resected at Children’s Minnesota over the last 3 years to evaluate our current practices. From 2019-2021, 118 patients with newly diagnosed CNS tumors underwent surgery followed by molecular assessment (14 IHC/FISH, 85 NGS, 7 methylation profiling) on 100% of medulloblastoma, other embryonal tumors, and schwannoma; 90% of ependymoma; 88% of HGG; 71% of LGG/glioneuronal/neuronal tumors; and 50% of meningioma and craniopharygioma. MAPK pathway alterations were seen in 84% of LGG/glioneuronal/neuronal tumors, with KIAA1540-BRAF fusion seen exclusively in pilocytic astrocytoma and BRAFV600E alterations seen in diffuse LGG (75%), PLNTY and PXA. Frequent alterations seen in HGG included H3F3A-K27M, H3F3A-G34, TP53, PDGFRA, ATRX, CDKN2A/B. Common gene alterations in medulloblastoma included monosomy 6 (100%) and alteration of CTNNB1 (50%) in WNT subgroup; PTCH1 (75%) in SHH subgroup; MYC/MYCN gain (60%) or amplification (60%) in Non-WNT/SHH subgroup. Alterations in FOXR2 in CNS neuroblastoma, SMARCB1 in ATRT and C19MC in ETMR confirmed these diagnoses. Supratentorial ependymoma showed ZFTQ-RELA fusion (100%) and infratentorial ependymoma showed chromosomal copy number changes including 1q gain (40%). Meningiomas showed deletion of NF2 and SMARCB1 and craniopharyngioma had alterations in CTNNB1. Molecular analysis confirmed the diagnosis in 23% of tumors, aided with targeted treatment in 20% of patients (82% of HGG, 9% of LGG, 13% of medulloblastomas) and allowed for risk-adapted treatment in 93% of medulloblastomas. These findings indicate that identification of pathogenic variants in CNS tumors aids in the diagnosis and treatment of pediatric CNS tumors and should be considered standard practice.
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molecular analysis
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