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PDGFRA gain in low-grade diffuse gliomas.

Kazuya Motomura1, Michel Mittelbronn, Werner Paulus

  • 1International Agency for Research on Cancer, Lyon, France.

Journal of Neuropathology and Experimental Neurology
|December 18, 2012
PubMed
Summary
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Platelet-derived growth factor receptor-α (PDGFRA) amplification is common in diffuse astrocytomas, often occurring with IDH1/2 mutations. This finding offers insights into glioma development and patient prognosis.

Area of Science:

  • Neuro-oncology
  • Cancer Genetics
  • Molecular Pathology

Background:

  • Glioblastomas with proneural signatures often have IDH1 mutations and PDGFRA amplification.
  • IDH1/2 mutations are early events in diffuse astrocytomas, precursors to secondary glioblastomas.
  • The role and timing of PDGFRA amplification in these precursor tumors remain unclear.

Purpose of the Study:

  • To investigate the frequency and significance of PDGFRA amplification in low-grade diffuse gliomas.
  • To explore the relationship between PDGFRA amplification, IDH1/2 mutations, and 1p/19q loss.
  • To assess the prognostic value of PDGFRA amplification in diffuse astrocytomas.

Main Methods:

  • Quantitative polymerase chain reaction (qPCR) was used to assess PDGFRA gain in 342 low-grade diffuse gliomas.

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  • Previously published data were analyzed to correlate PDGFRA gain with IDH1/2 mutations and 1p/19q loss.
  • Dual-color fluorescence in situ hybridization (FISH) was employed to examine PDGFRA and MET co-amplification patterns.
  • Main Results:

    • PDGFRA gain was detected in 16.3% of diffuse astrocytomas, significantly more than in oligodendrogliomas (2.6%).
    • PDGFRA gain showed an inverse correlation with IDH1/2 mutations and 1p/19q loss.
    • Diffuse astrocytomas frequently exhibited either IDH1/2 mutations or PDGFRA gain (93%).
    • Mean survival for diffuse astrocytoma patients with PDGFRA gain was 8.8 years, comparable to IDH1/2 or TP53 mutations, but longer than MET gain.
    • FISH analysis revealed PDGFRA and MET amplification in distinct cell populations, indicating intratumoral heterogeneity.

    Conclusions:

    • PDGFRA amplification is a frequent genetic event in diffuse astrocytomas, distinct from oligodendrogliomas.
    • The findings suggest PDGFRA amplification plays a role in diffuse astrocytoma development, potentially alongside IDH1/2 mutations.
    • PDGFRA amplification is associated with a favorable prognosis in diffuse astrocytomas.
    • Intratumoral heterogeneity, with distinct PDGFRA and MET amplification patterns, exists even in low-grade gliomas.