Table 3 Examples of key molecular alterations identified in the most common pediatric nervous system tumors, which could potentially be the focus of liquid biopsy-based mutation screening. Detection of these alterations in the liquid biome could facilitate diagnosis, classification of patients into molecular subgroups, qualification or disqualification from clinical trials, prediction of prognosis and detection of clonal evolution
From: Liquid biopsy for pediatric central nervous system tumors
Type of pediatric nervous system tumor | Molecular alterations | References |
|---|---|---|
High grade glioma—hemispheric | H3F3A G34R/V with alterations in: | |
ATRX/DAXX | ||
TP53 | ||
MYCN amplification | ||
BRAF V600E | ||
PDGFRA amplification | ||
SETD2 | ||
IDH | ||
BRAF V600E +/− CDKN2A/B | ||
NTRK1, 2, or 3 fusion (Infant HGG) | ||
High grade glioma—midline | H3F3A or HIST1H3B K27M with alterations in: | |
TP53 | ||
ATRX/DAXX (low frequency) | ||
FGFR1 (thalamic gliomas) | ||
NF1 | ||
PDGFRA amplification | ||
BRAF V600E +/− CDKN2A/B | ||
Atypical teratoid rhabdoid tumors (ATRT) | SMARCB1 | |
SMARCA4 (inactivating mutations or deletions) | ||
Low-grade gliomas (brain or spinal cord) | BRAF-KIAA fusion | |
BRAFV600E | ||
NF1 | ||
FGFR fusions, FGFR1 mutations, NTRK rearrangements | ||
Choroid plexus tumors | TP53 | |
Aneuploidy | ||
Chromosome gains or losses | ||
Medulloblastoma | Shh pathway alterations | |
Wnt pathway alterations | ||
Myc, MYCN amplification | ||
GLI2 amplification | ||
TP53 | ||
Ependymoma (papillary, clear cell, tanycytic, or anaplastic) | Supratentorial: RELA fusion,YAP fusion | |
Infratentorial: PFA vs PFB based on methylation profiles | ||
Spine/brain: NF2 | ||
Embryonal tumors with multilayered rosettes (ETMR) and other embryonal tumors | C19MC-amplification (miRNA cluster), or fusion with TTYH1 gene |
