Telomere length and Wnt/ß-catenin pathway in adamantinomatous craniopharyngiomas.

Objectives: To evaluate how telomere 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 aCP patients from 2 tertiary institutions. Methods: Clinicopathological features were retrieved from the 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 CTNNB1 mutations 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: 0.297-0.597vs 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 telomeres 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, demonstrating a relationship between the Wnt/ß-catenin pathway and telomere biology in the pathogenesis of aCPs.

Surgery for focal cortical dysplasia in children using intraoperative mapping.

OBJECTIVE: Children with malformation of cortical development represent a significant proportion of pediatric epilepsy surgery candidates. Here, we describe a single-center experience with pediatric patients who underwent surgery for intractable epilepsy due to focal cortical dysplasia (FCD). METHODS: Clinical data of 78 patients under 18 years of age with diagnosis of intractable epilepsy due to FCD who underwent surgery from January 1996 to January 2012 were reviewed comparing data of patients submitted to electrocorticography (ECoG) with those without ECoG. RESULTS: Patients' mean age at surgery was 8.52 ± 4.99 years; mean age at epilepsy onset was 2.55 ± 3.01 years. Almost 80 % of the patients underwent ECoG register that was essential for delimitation of surgical resection in 66 out of 78 patients. ECoG was performed in all patients with extratemporal lesions, and the most common FCD found was type II. Seizure outcome was similar in groups with or without ECoG. CONCLUSIONS: Tailored resection of FCD lesions for intractable epilepsy can be safely performed in children with a good seizure outcome and low complication rate. Epilepsy surgery should be considered for all patients with FCD and refractory epilepsy.