CIC inactivating mutations identify aggressive subset of 1p19q codeleted gliomas
Vincent Gleize1, Agusti Alentorn1,2, Léa Connen de Kérillis1
1Sorbonne Université, UPMC Univ Paris 06, Inserm, CNRS, UM 75, U 1127, UMR 7225, ICM, Paris, France.
Annals of Neurology
|May 29, 2015
Summary
Mutations in the CIC gene are linked to poorer outcomes in oligodendroglial tumors with 1p19q codeletion, driving faster tumor growth and inhibiting differentiation.
Area of Science:
- Neuro-oncology
- Cancer Genomics
- Molecular Biology
Background:
- The CIC gene is frequently mutated in oligodendroglial tumors, particularly those with 1p19q codeletion.
- The precise clinical and biological implications of CIC mutations in these tumors are not well understood.
Purpose of the Study:
- To investigate the clinical and biological impact of CIC gene mutations in oligodendroglial tumors.
- To analyze the association between CIC mutations, patient outcomes, and tumor molecular profiles.
Main Methods:
- Sequencing of the CIC gene in 127 oligodendroglial tumors (109 with 1p19q codeletion).
- Analysis of patient outcomes, MRI, transcriptomic profiles, and CIC protein expression.
- In vitro studies using a human glioma cell line to assess the functional impact of CIC mutations.
Main Results:
- 63 CIC mutations were identified in 60 patients, predominantly in 1p19q codeleted and IDH-mutated tumors.
- CIC mutations were significantly associated with poorer patient outcomes in both univariate and multivariate analyses.
- CIC mutant gliomas exhibited faster growth, enriched proliferative pathways, and altered expression of CIC target genes, including ETV1, ETV4, ETV5, and CCND1.
Conclusions:
- CIC mutations lead to CIC protein inactivation, promoting proliferation and inhibiting differentiation in 1p19q codeleted gliomas.
- These molecular alterations contribute to a poorer prognosis for patients with this specific glioma subtype.
- The study identifies key downstream targets of CIC, offering potential avenues for therapeutic intervention.
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