Methylation status of TP73 in meningiomas

Abstract Deletions at 1p are frequent in meningioma and represent a genetic marker associated with the genesis of atypical WHO grade II forms. Previous mutational analysis of TP73 , a structurally and functionally TP53 homologous gene located at 1p36.33, failed to demonstrate a significant rate of sequence variations linked to gene inactivation in meningiomas with 1p loss. As an alternative, TP73 may be inactivated through aberrant 5′ CpG island methylation, a primary mechanism participating in the inactivation of tumor suppressor genes during tumorigenesis. We determined the methylation status of the TP73 gene in a series of 60 meningiomas (33 grade I, 24 grade II, and 3 grade III samples), including tumors with deletion at 1p ( n =30) and with intact 1p ( n =30). Aberrant methylation was detected in 10 cases (33%) with 1p deletion and in 3 tumors (10%) with retention of alleles at this chromosome arm. The distribution of the 13 cases of methylation according to malignancy grade was 7 grade I, 5 grade II, and 1 grade III tumor. Accordingly, although TP73 aberrant methylation was more frequent in meningiomas with 1p deletion ( P TP73 expression in malignant meningiomas suggest that opposing functions of this gene may characterize distinct subsets of tumors: suppressed or reduced expression as a result of CpG methylation in some grade I–grade II tumors, and enhanced expression in some more malignant forms.