RESUMO
Glioblastoma (GBM) is a brain tumor that carries a dismal prognosis and displays considerable heterogeneity. We have recently identified recurrent H3F3A mutations affecting two critical amino acids (K27 and G34) of histone H3.3 in one-third of pediatric GBM. Here, we show that each H3F3A mutation defines an epigenetic subgroup of GBM with a distinct global methylation pattern, and that they are mutually exclusive with IDH1 mutations, which characterize a third mutation-defined subgroup. Three further epigenetic subgroups were enriched for hallmark genetic events of adult GBM and/or established transcriptomic signatures. We also demonstrate that the two H3F3A mutations give rise to GBMs in separate anatomic compartments, with differential regulation of transcription factors OLIG1, OLIG2, and FOXG1, possibly reflecting different cellular origins.
Assuntos
Neoplasias Encefálicas/genética , Epigênese Genética , Glioblastoma/genética , Histonas/genética , Isocitrato Desidrogenase/genética , Mutação , Adulto , Neoplasias Encefálicas/patologia , Criança , Metilação de DNA , Glioblastoma/patologia , Humanos , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , TranscriptomaRESUMO
Juvenile dermatomyositis (JDM) is a rare autoimmune vasculopathy affecting children and adolescents under the age of 18. In this report we describe an 8-year-old boy who, besides myopathy, presented with an uncommonly broad spectrum of skin findings that had evolved after summer holidays at the Mediterranean Sea. Upon treatment with intravenous methylprednisolone the patient's condition considerably improved. Our case report illustrates that JDM requires comprehensive evaluation and multidisciplinary management.
Assuntos
Dermatomiosite , Criança , Dermatomiosite/diagnóstico , Humanos , MasculinoRESUMO
Fungal infections are a leading cause of morbidity and mortality in severely immunocompromised patients and have been increasing in incidence in recent years. Invasive aspergillosis (IA) is the most common filamentous fungal infection and is, in adults as well as in children, difficult to diagnose. Several PCR assays to detect Aspergillus DNA have been established, but so far, studies on molecular tools for the diagnosis of IA in children are few. We evaluated the results of a nested PCR assay to detect Aspergillus DNA in clinical samples from paediatric and adolescent patients with suspected IA. Blood and non-blood samples from immunocompromised paediatric and adolescent patients with suspected invasive fungal infection were sent for processing Aspergillus PCR to our laboratory. PCR results from consecutive patients from three university children's hospitals investigated between November 2000 and January 2007 were evaluated. Fungal infections were classified according to the EORTC classification on the grounds of clinical findings, microbiology and radio-imaging results. Two hundred and ninety-one samples from 71 patients were investigated for the presence of Aspergillus DNA by our previously described nested PCR assay. Two, 3 and 34 patients had proven, probable and possible IA, respectively. Sensitivity (calculated from proven and probable patients, n=5) and specificity (calculated from patients without IA, n=32) rates of the PCR assay were 80 and 81 %, respectively. Our nested PCR assay was able to detect Aspergillus DNA in blood, cerebrospinal fluid and bronchoalveolar lavage samples from paediatric and adolescent patients with IA with high sensitivity and specificity rates.
