Genetic and epigenetic alterations in meningiomas

Abstract

Meningiomas originate from the arachnoid layer of the meninges and divided histologically into three grades: benign (grade I), atypical (grade II), and malignant meningiomas (grade III). Genetic alterations in grade I meningiomas include frequent deletions of chromosomal locus 22q12 and NF2 gene mutations and uncommon somatic SMARCB1 and SMARCE1gene mutations; In grade II meningiomas, chromosomal losses occur on 1p, 22q, 14q, 18q, 10, and 6q, and gains on 20q, 12q, 15q, 1q, 9q, and 17q; In grade III meningiomas, losses have been recognized on 6q, 10, and 14q and alterations of PTEN, CDKN2A and CDKN2B genes. Epigenetic alterations in meningiomas include hypermethylation of the tumor suppressor genes p73 in grade I meningiomas and TIMP3 GSTP1, MEG3, HOXA6, HOXA9, PENK, WNK2 and UPK3A genes with an increasing frequency according to grade. Abnormal expression of IGF signaling family genes and Wnt signaling pathway is associated with meningioma progression. MiRNA expression profiling of meningiomas show downregulation of miR-29c-3p, miR-200a, miR-145 and miR- 219-5p and upregulation of miR-21 miR-335 and miR-190a levels. In conclusion, extensive genetic and epigenetic alterations exist in meningiomas that may help assessing prognosis. In addition, since miRNA expression may be modified by artificial miRNAs, new effective therapeutic strategies may be developed especially for resistant or high grade meningiomas.