In:
Acta Neuropathologica, Springer Science and Business Media LLC, Vol. 141, No. 2 ( 2021-02), p. 281-290
Abstract:
Clear cell meningioma represents an uncommon variant of meningioma that typically affects children and young adults. Although an enrichment of loss-of-function mutations in the SMARCE1 gene has been reported for this subtype, comprehensive molecular investigations are lacking. Here we describe a molecularly distinct subset of tumors ( n = 31), initially identified through genome-wide DNA methylation screening among a cohort of 3093 meningiomas, of which most were diagnosed histologically as clear cell meningioma. This cohort was further supplemented by an additional 11 histologically diagnosed clear cell meningiomas for analysis ( n = 42). Targeted DNA sequencing revealed SMARCE1 mutations in 33/34 analyzed samples, accompanied by a nuclear loss of expression determined via immunohistochemistry and a decreased SMARCE1 transcript expression in the tumor cells. Analysis of time to progression or recurrence of patients within the clear cell meningioma group ( n = 14) in comparison to those with meningioma WHO grade 2 ( n = 220) revealed a similar outcome and support the assignment of WHO grade 2 to these tumors. Our findings indicate the existence of a highly distinct epigenetic signature of clear cell meningiomas, separate from all other variants of meningiomas, with recurrent mutations in the SMARCE1 gene. This suggests that these tumors may arise from a different precursor cell population than the broad spectrum of the other meningioma subtypes.
Type of Medium:
Online Resource
ISSN:
0001-6322
,
1432-0533
DOI:
10.1007/s00401-020-02247-2
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
1458410-4