ABSTRACT
INTRODUCTION: Studies addressing the methylation pattern in adamantinomatous craniopharyngioma (ACP) are lacking. OBJECTIVE: To identify methylation signatures in ACPs regarding clinical presentation and outcome. METHODS: Clinical and pathology data were collected from 35 patients with ACP (54% male; 18.1 years [2-68]). CTNNB1 mutations and methylation profile (MethylationEPIC/Array-Illumina) were analyzed in tumoral DNA. Unsupervised machine learning analysis of this comprehensive methylome sample was achieved using hierarchical clustering and multidimensional scaling. Statistical associations between clusters and clinical features were achieved using the Fisher test and global biological process interpretations were aided by Gene Ontology enrichment analyses. RESULTS: Two clusters were revealed consistently by all unsupervised methods (ACP-1: n = 18; ACP-2: n = 17) with strong bootstrap statistical support. ACP-2 was enriched by CTNNB1 mutations (100% vs 56%, P = .0006), hypomethylated in CpG island, non-CpG Island sites, and globally (P < .001), and associated with greater tumor size (24.1 vs 9.5 cm3, P = .04). Enrichment analysis highlighted pathways on signaling transduction, transmembrane receptor, development of anatomical structures, cell adhesion, cytoskeleton organization, and cytokine binding, and cell type-specific biological processes as regulation of oligodendrocytes, keratinocyte, and epithelial cells differentiation. CONCLUSION: Two clusters of patients with ACP were consistently revealed by unsupervised machine learning methods, with one of them significantly hypomethylated, enriched by CTNNB1 mutated ACPs, and associated with increased tumor size. Enrichment analysis reinforced pathways involved in tumor proliferation and in cell-specific tumoral microenvironment.
Subject(s)
Craniopharyngioma , DNA Methylation , Epigenesis, Genetic , Pituitary Neoplasms , beta Catenin , Humans , Craniopharyngioma/genetics , Craniopharyngioma/pathology , Male , Female , Pituitary Neoplasms/genetics , Pituitary Neoplasms/pathology , Adolescent , Adult , Child , Middle Aged , Young Adult , beta Catenin/genetics , beta Catenin/metabolism , Child, Preschool , Aged , Mutation , CpG Islands/genetics , Gene Expression Regulation, NeoplasticABSTRACT
Phenotypic divergence among population genotypes is useful to improve our knowledge about how to preserve the genetic resource available. The aim of this study was to evaluate the phenotypic divergence among jabuticaba genotype trees in relation to stem and primary shoot length analyzed in three consecutives productive cycles. The genotypes of jabuticaba trees were obtained from Fruteiras Nativas collection of Universidade Tecnológica Federal do Paraná (UTFPR Campus Dois Vizinhos, Parana State, Brazil). The genotypes had their origin in forest fragments of the Southwest Region of Paraná and Minas Gerais State (Brazil). Phenotypic divergence was performed through analysis of variance (ANOVA), Mahalanobis distance, Tocher optimization cluster analysis and by the nearest neighbor method. The results obtained showed that the diversity among the genotypes were different according to the cycle analyzed since we obtained different groups for each year analyzed. Genotypes from Minas Gerais tended to remain in distinct groups, since it had low similarity with the others. The genotype 'Vitorino' had a high divergence among individuals from the same place.(AU)
A divergência fenotípica entre os genótipos de uma população é útil para que se tenha conhecimento sobre formas de conservação dos recursos genéticos disponíveis. O objetivo deste estudo foi avaliar a divergência fenotípica entre os genótipos de jabuticabeira em relação ao comprimento do caule e de brotações analisados em três ciclos produtivos consecutivos. Os genótipos de jabuticabeiras foram obtidos da coleção de Fruteiras Nativas da Universidade Tecnológica Federal do Paraná (UTFPR - Campus Dois Vizinhos, Paraná, Brasil). Os materiais são originários de fragmentos florestais da Região Sudoeste do Paraná e do Estado de Minas Gerais. A divergência fenotípica foi caracterizada por meio das análises de variância (ANOVA), distância de Mahalanobis, de análise de agrupamento de otimização de Tocher e pelo método do vizinho mais próximo. Os resultados obtidos demonstraram que a diversidade entre os genótipos foi diferente conforme o ciclo analisado, pois em cada ano houve a formação de grupos diferentes. Os genótipos provenientes de Minas Gerais tenderam a se manter em grupos distintos, já que possuíram baixa similaridade com os demais. O genótipo Vitorino apresentou alta divergência entre indivíduos do mesmo local.(AU)
Subject(s)
Myrtaceae/growth & development , Myrtaceae/genetics , Biological Variation, Population , Analysis of VarianceABSTRACT
Phenotypic divergence among population genotypes is useful to improve our knowledge about how to preserve the genetic resource available. The aim of this study was to evaluate the phenotypic divergence among jabuticaba genotype trees in relation to stem and primary shoot length analyzed in three consecutives productive cycles. The genotypes of jabuticaba trees were obtained from Fruteiras Nativas collection of Universidade Tecnológica Federal do Paraná (UTFPR Campus Dois Vizinhos, Parana State, Brazil). The genotypes had their origin in forest fragments of the Southwest Region of Paraná and Minas Gerais State (Brazil). Phenotypic divergence was performed through analysis of variance (ANOVA), Mahalanobis distance, Tocher optimization cluster analysis and by the nearest neighbor method. The results obtained showed that the diversity among the genotypes were different according to the cycle analyzed since we obtained different groups for each year analyzed. Genotypes from Minas Gerais tended to remain in distinct groups, since it had low similarity with the others. The genotype 'Vitorino' had a high divergence among individuals from the same place.
A divergência fenotípica entre os genótipos de uma população é útil para que se tenha conhecimento sobre formas de conservação dos recursos genéticos disponíveis. O objetivo deste estudo foi avaliar a divergência fenotípica entre os genótipos de jabuticabeira em relação ao comprimento do caule e de brotações analisados em três ciclos produtivos consecutivos. Os genótipos de jabuticabeiras foram obtidos da coleção de Fruteiras Nativas da Universidade Tecnológica Federal do Paraná (UTFPR - Campus Dois Vizinhos, Paraná, Brasil). Os materiais são originários de fragmentos florestais da Região Sudoeste do Paraná e do Estado de Minas Gerais. A divergência fenotípica foi caracterizada por meio das análises de variância (ANOVA), distância de Mahalanobis, de análise de agrupamento de otimização de Tocher e pelo método do vizinho mais próximo. Os resultados obtidos demonstraram que a diversidade entre os genótipos foi diferente conforme o ciclo analisado, pois em cada ano houve a formação de grupos diferentes. Os genótipos provenientes de Minas Gerais tenderam a se manter em grupos distintos, já que possuíram baixa similaridade com os demais. O genótipo Vitorino apresentou alta divergência entre indivíduos do mesmo local.