ReviewCancer

Molecular mechanisms and therapeutic targets in pediatric brain tumors

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Sci. Signal.  14 Mar 2017:
Vol. 10, Issue 470, eaaf7593
DOI: 10.1126/scisignal.aaf7593

Figures

  • Fig. 1 Synopsis of signaling pathway alterations and potential drug targets in molecular subgroups of pediatric MB.

    Gain- or loss-of-function aberrations in pathway components that have been identified within distinct molecular subgroups of MB. Candidates for targeted therapy are indicated, including information on the current developmental stage of potential drugs.

    CREDIT: K. SUTLIFF/SCIENCE SIGNALING
  • Fig. 2 Synopsis of signaling pathway alterations and potential drug targets in molecular subgroups of pediatric EPN.

    Gain- or loss-of-function aberrations in pathway components that have been identified within distinct molecular subgroups of EPN. Candidates for targeted therapy are indicated, including information on the current developmental stage of potential drugs.

    CREDIT: K. SUTLIFF/SCIENCE SIGNALING
  • Fig. 3 Synopsis of signaling pathway alterations and potential drug targets in molecular subgroups of pediatric HGG.

    Gain- or loss-of-function aberrations in pathway components that have been identified within distinct molecular subgroups of HGG. Candidates for targeted therapy are indicated, including information on the current developmental stage of potential drugs.

    CREDIT: K. SUTLIFF/SCIENCE SIGNALING

Tables

  • Table 1 MB molecular subgroups.

    Summary of key features of the four subgroups of MB, defined on the basis of gene expression and DNA methylation. LCA, large cell/anaplastic; DNMB, desmoplastic/nodular medulloblastoma; SVZ, subventricular zone; NSC, neural stem cell; RT, radiotherapy.

  • Table 2 Molecular and clinical characteristics of ependymal tumor subgroups.

    Summary of key molecular and clinical findings in the nine molecular subgroups of ependymal tumors as identified by methylation profiling. CIN, chromosomal instability. I, infant; C, children; A, adults; M, male; F, female.

  • Table 3 Clinicopathological features of pediatric HGG subgroups.

    Summary of major molecular and clinical characteristics of pediatric HGG subgroups as defined by a combination of DNA methylation profiles and genetic alterations. amp, amplification; del, deletion; mut, mutated; NA, as yet unclear; OS, overall survival; wt, wild type.

    Methylation
    subgroup
    IDH mutK27 mutG34 mutHistone/IDH wt
    Further
    specification
    H3.1 K27MH3.3 K27MH3.3 G34R/VMYCNPDGFRAEGFROthers
    LocationHemispheric,
    mostly
    frontal lobe
    Almost
    exclusively
    pons (DIPG)
    Midline
    (thalamus,
    cerebellum, spine)
    pons (DIPG)
    HemisphericHemisphericHemisphericHemisphericHemispheric
    Average ageTeenage/young
    adult
    ~4.5 years~7 yearsTeenage/young
    adult
    ~8 years~11 years~10 yearsNA
    PrognosisIntermediate
    median
    OS >5 years
    Poor median
    OS ~15 months
    Very poor
    median OS
    ~10 months
    Poor median
    OS ~24 months
    Poor median
    OS ~14 months
    Poor median
    OS ~21 months
    Intermediate
    median OS
    ~44 months
    NA
    MutationsIDH1, TP53,
    ATRX
    HIST1H3A/B/C,
    TP53, PPM1D,
    ACVR1, PIK3R1,
    PIK3CA
    H3F3A, TP53,
    PPM1D, ATRX,
    PI3KR1, PIK3CA,
    NF1, FGFR1, BRAF
    H3F3A, TP53,
    ATRX, PDGFRA
    TP53TP53TP53TP53, PTEN,
    PIK3CA
    Copy number
    aberrations
    CCND/CDK amp
    CDKN2A/B del
    Various RTK amp
    CCND/CDK amp
    PDGFRA ampMYCN amp ID2
    amp CDK4/6
    amp Chr7 gain
    PDGFRA
    amp
    EGFR amp
    CDKN2A/B del
    10q del
    MET fusion/
    amp NTRK
    fusion
    Other featuresMGMT methylation
    occasional
    hypermutation
    phenotype
    Global H3
    K27me3 loss
    Global H3
    K27me3 loss
    MGMT methylation
    subtelomeric
    hypomethylation
    NANANANA