RESUMO
Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/ß-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.
Assuntos
Neoplasias do Sistema Nervoso Central , Tumores Neuroectodérmicos Primitivos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Proteínas de Ciclo Celular/genética , Neoplasias do Sistema Nervoso Central/genética , Metilação de DNA , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Tumores Neuroectodérmicos Primitivos/genética , Proteínas de Ligação a RNA/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/genética , Via de Sinalização Wnt/genéticaRESUMO
Infants with acute lymphoblastic leukaemia (ALL) have a high frequency of central nervous system (CNS) involvement. Flow cytometric analysis of cerebrospinal fluid (CSF) was recently demonstrated to be a sensitive method for detecting CNS involvement in childhood ALL. In the present study, CSF from 14 infants was collected at routine lumbar punctures and analysed by multicolour flow cytometry. At initial diagnosis, leukaemic blasts were detected in CSF by flow cytometry in 11 patients (78·6%) compared to seven patients (50%) by cytospin. Larger studies are needed to determine if CSF flow cytometry has prognostic value in infant ALL.
Assuntos
Líquido Cefalorraquidiano/citologia , Citometria de Fluxo/métodos , Infiltração Leucêmica/diagnóstico , Células-Tronco Neoplásicas/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/líquido cefalorraquidiano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , RecidivaRESUMO
The number of long-term survivors after cancer therapy in childhood and young adulthood is increasing. Accordingly, life-long follow-up of significant health problems related to the given cancer therapy is needed as only one third of the survivors will remain free of any physical or psychosocial late effects. At present, national activity is needed to establish a uniform follow-up clinic service to support education, diagnostics, therapy and rehabilitation of these long-term adverse effects after cancer therapy at young age.
Assuntos
Continuidade da Assistência ao Paciente/organização & administração , Oncologia/organização & administração , Neoplasias/terapia , Sobreviventes , Adolescente , Adulto , Criança , Intervalo Livre de Doença , Humanos , Qualidade de Vida , Fatores de RiscoRESUMO
The combination of the Portable Microbe Enrichment Unit (PMEU) cultivation and ChemPro100i((R)) Chemical Detector helps the fast detection of hospital infections. The first alarm of the microbe metabolism and growth in the enrichment culture was achieved in 2-3h when pure cultures of strains isolated from neonatal patients were tested. For the detection of minor concentrations of the bacteria, Bacillus, Staphylococcus, Klebsiella and Escherichia strains were diluted to 0.5-600cells per ml. Their preliminary detection was achieved within 4-5h. The combination of enrichment culture (PMEU) and detection of bacterial products by ion mobility spectrometer is a rapid and sensitive method for diagnosis of bacterial growth. This finding warrants further studies with clinical samples.