ODP354 Telomeres Length and Wnt/beta-catenin Pathway in Adamantinomatous Craniopharyngiomas

Abstract

Abstract Objectives To evaluate how telomeres length behaves in adamantinomtous craniopharyngioma (aCP) and if it contributes to the pathogenesis of aCPs with and without CTNNB1 mutations. Design: Retrospective cross-sectional study enrolling 42 aCPpatients from two tertiary institutions. Methods Clinicopathological features were retrieved from patient's charts. Fresh frozen tumors were used for RNA and DNA analyses. Telomere length was evaluated by qPCR (T/S ratio). Somatic mutations in TERT promoter (TERTp) and CTNNB1 were detected by Sanger and/or whole-exome sequencing. We performed RNA-Seq to identify differentially expressed genes in aCPs presenting with shorter or longer telomere lengths. Results Mutations in CTNNB1 were detected in 29 (69%) tumors. There was higher frequency of CTNNB1mutations in aCPs from patients diagnosed under the age of 15 years (85% vs 15%; p=0. 04) and a trend to recurrent disease (76% vs 24%; p=0.1). No mutation was detected in the TERTp region. The telomeres were shorter in CTNNB1-mutated aCPs (0.441, IQR: 0.297-0.597 vs 0.607, IQR: 0.445-0.778; p=0. 04) but it was neither associated with clinicopathological features nor with recurrence. RNAseq identified a total of 387 differentially expressed genes, generating two clusters, being one enriched for short telomere and CTNNB1-mutated aCPs. Conclusions CTNNB1 mutations are more frequent in children and adolescents and appear to associate with progressive disease. CTNNB1-mutated aCPs have shorter telomeres. This is the first evidence for a relationship between the Wnt/beta-catenin pathway and telomere biology in the pathogenesis of aCPs. Presentation: No date and time listed