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Loss of SMARCB1/INI1 Immunoexpression in Chordoid Meningiomas
Prit B Malgulwar1, Aanchal Kakkar1, Mehar C Sharma1
1Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
Background:
Chordoid meningiomas have an aggressive clinical course characterized by frequent recurrences. Recent whole-genome sequencing studies demonstrated Chr22 loss in chordoid meningiomas not accounted for by NF2 mutations. SMARCB1/INI1 is a candidate gene on Chr22, which has not been analyzed extensively in meningiomas. AKT1 mutation has been recently identified to be a driver of meningiomagenesis.
Materials And Methods:
Cases of chordoid meningioma were retrieved along with meningiomas of other subtypes for comparison. INI1 immunohistochemistry was performed. SMARCB1 and AKT1 were analyzed by sequencing.
Results:
Sixteen chordoid meningiomas were identified (1.1% of all meningiomas). Six cases (37.5%) showed loss of INI1 immunoexpression. All other meningioma subtypes (n = 16) retained INI1 immunoexpression. AKT1 E17K mutation was identified in one case (16.7%). Notably, SMARCB1 mutations were not identified in any of the chordoid meningiomas analyzed, including those showing INI1 loss immunohistochemically.
Conclusion:
This is the first study to demonstrate loss of SMARCB1/INI1 immunoexpression in chordoid meningiomas, adding to the tumors with INI1 loss. However, in absence of INI1 mutation, mechanisms for INI1 loss require further evaluation. Identification of AKT1 mutation opens up new avenues for targeted therapy in patients with such aggressive tumors.
Insights
Chordoid meningiomas show loss of SMARCB1/INI1 immunoexpression, distinct from NF2 mutations. AKT1 mutations were identified, offering potential for targeted therapies in these aggressive tumors.
Area of Science:
- Neuro-oncology
- Genetics
- Cancer Biology
Background:
- Chordoid meningiomas exhibit aggressive behavior and frequent recurrences.
- Whole-genome sequencing revealed Chr22 loss in chordoid meningiomas, independent of NF2 mutations.
- SMARCB1/INI1 on Chr22 and AKT1 mutations are implicated in meningiomagenesis.
Purpose of the Study:
- To investigate SMARCB1/INI1 and AKT1 alterations in chordoid meningiomas.
- To compare these alterations with other meningioma subtypes.
Main Methods:
- Retrieved cases of chordoid meningioma and other meningioma subtypes.
- Performed INI1 immunohistochemistry.
- Analyzed SMARCB1 and AKT1 genes by sequencing.
Main Results:
- Sixteen chordoid meningiomas were identified (1.1%).
- Loss of INI1 immunoexpression was observed in 37.5% of chordoid meningiomas, but not in other subtypes.
- AKT1 E17K mutation was found in one case (16.7%); SMARCB1 mutations were absent.
Conclusions:
- This study is the first to report loss of SMARCB1/INI1 immunoexpression in chordoid meningiomas.
- Mechanisms underlying INI1 loss in the absence of mutation require further investigation.
- AKT1 mutation identification presents new therapeutic targets for aggressive meningiomas.
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