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Capicua (CIC) mutations in gliomas in association with MAPK activation for exposing a potential therapeutic target

Sourat Darabi1, Joanne Xiu2, Timothy Samec3

  • 1Hoag Family Cancer Institute, Newport Beach, CA, USA.

Medical Oncology (Northwood, London, England)
|June 8, 2023
PubMed

Insights

Capicua (CIC) gene mutations are common in oligodendroglioma and indicate increased MAPK pathway activation. Identifying CIC mutations can guide targeted MEK/MAPK inhibitor therapies for improved glioma patient survival.

Area of Science:

  • Neuro-oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Gliomas represent the most common primary brain tumors in the USA, characterized by aggressive behavior and limited therapeutic options.
  • Effective treatment strategies necessitate a comprehensive understanding of the genetic landscape and pathway dysregulation driving glioma development.
  • The Capicua (CIC) gene, a known tumor and transcriptional suppressor, plays a critical role in cellular regulation.

Purpose of the Study:

  • To investigate the mutation prevalence of the Capicua (CIC) gene in various glioma subtypes.
  • To assess the relationship between CIC gene mutations and Mitogen-Activated Protein Kinase (MAPK) pathway activation in clinical glioma tissues.
  • To evaluate the potential of CIC as a predictive biomarker for targeted therapy selection in gliomas.

Main Methods:

  • Molecular profiling of clinical glioma tissue samples.
  • Analysis of Capicua (CIC) gene mutation status.
  • Assessment of MAPK pathway activation levels.
  • Correlation analysis between CIC mutations and MAPK pathway activity across different glioma subtypes.

Main Results:

  • CIC mutations were identified in 52.1% of oligodendrogliomas, significantly higher than in low-grade astrocytomas or glioblastomas.
  • CIC mutations were present across all glioma subtypes studied.
  • MAPK pathway mutations were more frequent in CIC wild-type gliomas, irrespective of subtype.
  • MAPK pathway activation was notably enhanced in CIC-mutated oligodendrogliomas.

Conclusions:

  • The Capicua (CIC) gene serves as a relevant genetic marker for predicting MAPK pathway activation in gliomas.
  • The presence or absence of CIC mutations can inform the selection and development of MEK/MAPK-inhibitory clinical trials.
  • Utilizing CIC mutation status may enhance patient outcomes by enabling more precise, targeted therapeutic interventions.
Keywords:
CapicuaClinical oncologyGliomaMAPKMolecular oncologyTargeted medicine

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