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MerlinS13 phosphorylation regulates meningioma Wnt signaling and magnetic resonance imaging features

Charlotte D Eaton1,2,3, Lauro Avalos2,4, S John Liu1,2,3

  • 1Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.

Nature Communications
|September 9, 2024
PubMed

Insights

Merlin-intact meningiomas grow due to Merlin serine 13 dephosphorylation activating Wnt signaling. High apparent diffusion coefficient (ADC) on MRI may indicate favorable outcomes for these tumors.

Area of Science:

  • Neuro-oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Meningiomas often involve NF2/Merlin inactivation, but some retain Merlin expression.
  • Mechanisms of Merlin-intact meningioma growth and non-invasive biomarkers are poorly understood.
  • Current understanding lacks biomarkers for guiding treatment de-escalation or imaging surveillance in Merlin-intact meningiomas.

Purpose of the Study:

  • To elucidate biochemical mechanisms driving Merlin-intact meningioma growth.
  • To identify an imaging biomarker for Merlin-intact meningiomas.
  • To correlate molecular findings with clinical outcomes and imaging characteristics.

Main Methods:

  • Single-cell RNA sequencing and proximity-labeling proteomic mass spectrometry.
  • Mechanistic and functional studies in xenografts and patient samples.
  • Magnetic resonance imaging (MRI) analysis, including apparent diffusion coefficient (ADC) measurements.

Main Results:

  • Merlin serine 13 (S13) dephosphorylation promotes Wnt signaling and meningioma growth by affecting β-catenin interactions.
  • Merlin-intact meningiomas with S13 phosphorylation correlate with favorable clinical outcomes.
  • High ADC values on MRI are associated with Merlin-intact meningiomas exhibiting S13 phosphorylation and favorable outcomes.

Conclusions:

  • Merlin S13 dephosphorylation is a key driver of Wnt signaling in Merlin-intact meningiomas.
  • Apparent diffusion coefficient (ADC) on MRI may serve as a non-invasive biomarker for Merlin-intact meningiomas.
  • These findings could guide treatment de-escalation and imaging surveillance strategies for specific meningioma subtypes.

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