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1.
Cancer Cell ; 32(4): 520-537.e5, 2017 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-28966033

RESUMO

We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification.


Assuntos
Neoplasias do Tronco Encefálico/genética , Glioma/genética , Histonas/genética , Mutação , Adolescente , Neoplasias do Tronco Encefálico/patologia , Proteínas de Ciclo Celular/genética , Criança , Pré-Escolar , DNA Topoisomerases Tipo I/genética , Exoma , Proteínas F-Box/genética , Proteína 7 com Repetições F-Box-WD , Feminino , Dosagem de Genes , Glioma/patologia , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Ubiquitina-Proteína Ligases/genética , Adulto Jovem
2.
Methods Mol Biol ; 1467: 61-71, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27417959

RESUMO

The embryonic epicardium is an important source of cardiovascular precursor cells and paracrine factors required for adequate heart formation. During embryonic heart formation, WT1 is mainly expressed in epicardial cells and epicardial derived cells. Its expression has been used to trace epicardial derivatives in embryos and recently it has been used to follow the reactivation of epicardial cells after myocardial infarction. Interestingly, the highest level of expression of WT1 during epicardium development correlates with the highest proliferative state, stem cell properties, and migratory capacity of epicardial cells. Here, we review the various types of tools and strategies used to study WT1 function in the embryonic epicardium and provide examples of their use.


Assuntos
Pericárdio/citologia , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Biologia de Sistemas/métodos , Animais , Movimento Celular , Proliferação de Células , Separação Celular , Células Cultivadas , Citometria de Fluxo , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Pericárdio/embriologia , Pericárdio/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Proteínas WT1
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