Hypermethylation and transcriptional downregulation of the TIMP3 gene is associated with allelic loss on 22q12.3 and malignancy in meningiomas.

摘要: The gene for the tissue inhibitor of metalloproteinase 3 (TIMP3) on 22q12.3 had been reported to be inactivated by promoter methylation in various types cancers, with controversial findings meningiomas. We performed direct sodium bisulfite sequencing a series 50 meningiomas, including 27 benign meningiomas [World Health Organization (WHO) grade I], 11 atypical (WHO II) and 12 anaplastic III), found hypermethylation TIMP3 67% but only 22% 17% Moreover, scores were significantly inversely correlated mRNA expression levels (P = 0.0123), treatment meningioma cell line Ben-Men-1 demethylating agents induced an increased expression. is located chromosomal band 22q12, allelic loss which occurs early tumorigenesis preferentially targets NF2 tumor suppressor gene. In our panel, all hypermethylation--except single case--exhibited losses 22q12.3. Thus, inactivation seems fairly exclusive 22q12 but--in contrast mutation--appears involved progression as it associated more aggressive, high-grade phenotype.