Molecular profiling of pediatric brain tumors: insight into biology and treatment.
ABSTRACT Recent history has witnessed unparalleled advances in our understanding of tumor biology, owing in large part to the publication of the human genome project. Paired with improvements in microarray technologies, the combination of genetic and expression profiles provides a unique opportunity to further enhance our understanding of the underlying mechanisms that drive tumor growth. Thus, integrated analysis of identified molecular changes with clinical and histologic data may further delineate a new risk stratification system for pediatric brain tumors, allowing more patient-tailored therapy and molecular-based therapeutic interventions.
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ABSTRACT: Brain tumors are the most common solid tumor diagnosed in childhood that account for significant morbidity and mortality. New therapies are urgently needed; hence, we conducted the first ever prospective open-label phase II trials of the biological response modifier, poly-ICLC, in children with brain tumors. Poly-ICLC is a synthetic double-stranded RNA that has direct antiviral, antineoplastic, and immune adjuvant effects. A total of 47 children representing a variety of brain tumor histopathologic subtypes were treated with poly-ICLC. On the basis of the results of the initial phase II trial, an expanded prospective phase II trial in low-grade glioma (LGG) has been initiated. MRI was used to acquire volume-based measures of tumor response. No dose-limiting toxicities have been observed. In the initial study 3 of 12 subjects with progressive high-grade gliomas (HGGs) responded, and 2 of 4 children with progressive LGG experienced stable disease for 18 to 24 months. In the follow-up LGG phase II study, 2 of 5 LGG patients were stable over 18 months, with 1 stable for 6 months. Overall 5 of 10 LGG patients have responded. On the basis of low toxicity and the promising LGG response, poly-ICLC may be effective for childhood LGG, and the results justify biomarker studies for personalization of poly-ICLC as a single agent or adjuvant.Journal of Pediatric Hematology/Oncology 12/2013; · 0.96 Impact Factor
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ABSTRACT: Background High-grade gliomas (HGGs) account for 15% of all pediatric brain tumors and are a leading cause of cancer-related mortality and morbidity. Pediatric HGGs (pHGGs) are histologically indistinguishable from their counterpart in adulthood. However, recent investigations indicate that differences occur at the molecular level, thus suggesting that the molecular path to gliomagenesis in childhood is distinct from that of adults. MicroRNAs (miRNAs) have been identified as key molecules in gene expression regulation, both in development and in cancer. miRNAs have been investigated in adult high-grade gliomas (aHGGs), but scant information is available for pHGGs.Methods We explored the differences in microRNAs between pHGG and aHGG, in both fresh-frozen and paraffin-embedded tissue, by high-throughput miRNA profiling. We also evaluated the biological effects of miR-17-92 cluster silencing on a pHGG cell line.ResultsComparison of miRNA expression patterns in formalin versus frozen specimens resulted in high correlation between both types of samples. The analysis of miRNA profiling revealed a specific microRNA pattern in pHGG with an overexpression and a proliferative role of the miR-17-92 cluster. Moreover, we highlighted a possible quenching function of miR-17-92 cluster on its target gene PTEN, together with an activation of tumorigenic signaling such as sonic hedgehog in pHGG.Conclusions Our results suggest that microRNA profiling represents a tool to distinguishing pediatric from adult HGG and that miR-17-92 cluster sustains pHGG.Neuro-Oncology 12/2013; · 5.29 Impact Factor
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ABSTRACT: Intramedullary ependymomas constitute the most frequent type of intramedullary tumor. In patients with neurofibromatosis type 2 (NF2), multiple intramedullary ependymomas are known to occur. In the non-NF2 population, however, the presence of multiple synchronous intramedullary ependymomas is exceedingly rare. In this article, the authors report the second case in the literature of multiple primary synchronous intramedullary ependymomas. To the best of the authors knowledge, this report represents the first to provide a detailed pathology of all lesions, thereby giving an added level of confidence on the primary synchronous nature of the lesions. The authors have also performed a review of the literature regarding multifocal intramedullary ependymomas. A review article and case report. The concomitant localization of two primary intramedullary spinal cord ependymomas in the setting of nongenetic predisposition is an uncommon phenomenon. In this article, the authors present the second report of multiple, synchronous intramedullary ependymomas. A detailed review of the literature reveals that the presence of multiple intramedullary lesions in non-NF2 patients is both rare and deserving of further study.The spine journal: official journal of the North American Spine Society 08/2013; · 2.90 Impact Factor