Promoter hypermethylation of genes encoding for RASSF/Hippo pathway members reveals specific alteration pattern in diffuse gliomas

Publication date: Available online 2 May 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Guénaëlle Levallet, Christian Creveuil, Lien Bekaert, Elodie Péres, Gaëtane Planchard, Sylvie Lecot-Cotigny, Jean-Sébastien Guillamo, Evelyne Emery, Gérard Zalcman, Emmanuèle Lechapt-ZalcmanRASSF/Hippo pathway alterations are poorly characterized in diffuse gliomas. We assayed promoter methylation of LATS1/2, MST1(STK4)/MST2(STK3), RASSF1, RASSF2, Nore1A/RASSF5, RASSF6, and RASSF10 genes in 133 diffuse Grade II-III-IV gliomas, using methylation-specific PCR or PCR coupled to Cobra. RASSF/Hippo pathway was highly silenced in gliomas, particularly RASSF1A (79.4%) and LATS2 (35.9%). Most gliomas (75.2%) exhibited at least hypermethylation for two promoters of the RASSF/Hippo member’s genes. The most frequent combination of promoter hypermethylation of one RASSF gene and one Hippo pathway member’s gene was RASSF1/LATS2-coupled hypermethylation (n=44, 33.08%). Hypermethylated profiles were related to IDH mutation, yet not randomly in IDH-mutated gliomas, since LATS2 promoter hypermethylation was more frequent in oligodendroglioma than in astrocytoma. RASSF1 and LATS2 promoter hypermethylation predicted a longer overall survival (OS). Considering hypermethylation of these two promoters, Cox regression analysis categorized the patients into three prognostic groups: i) high-risk (n=24, both RASSF1 and LATS2 unmethylated promoters, median OS=13 months); ii) intermediate-risk ...
Source: The Journal of Molecular Diagnostics - Category: Pathology Source Type: research