An integrated approach to identifying clinically relevant targets in pediatric gliomas.

摘要: 303 ISSN 2045-0907 10.2217/CNS.13.21 © 2013 Future Medicine Ltd CNS Oncol. (2013) 2(4), 303–306 High-grade gliomas (HGGs) are categorized by WHO as grade III–IV glial malignancies and account for roughly 15–20% of all pediatric tumors [1]. For patients diagnosed with supratentorial HGGs, the 2-year survival rates range from 10 to 30%. The prognosis diffuse brainstem is even more dismal, less than 10% will survive 2 years after diagnosis current treatment newly HGGs safe maximal surgical resection radiotherapy. addition chemotherapy this regimen debatable, reflecting lack consensus among neuro-oncologists regarding optimal protocol/treatment plan [2]. Despite these efforts, marginal impact has been made on overall patients. This begs question: ‘how do we change way in which view treat HGGs?’ To fully understand complexities subsequently identify therapeutic vulnerabilities, must first full molecular, cellular physiological context malignancies. While it long thought that both adult same disease affecting different patient populations, recently, multiple groups including Canadian Paediatric Cancer Genome Consortium St Jude Children’s Research Hospital–Washington University Louis Pediatric Project have challenged notion revealing striking differences mutation spectrum frequencies between [3–11]. use high-resolution genomic approaches uncovered potential targets such PDGFRA, MET IGF1R (recurrent focal amplification pontine gliomas) [7,10,12], BRAF CDK2NA (BRAF-V600E mutations concomitant CDKN2A loss a subset malignant astrocytomas) [11] FGFR1 (intragenic duplications tyrosine kinase domain low-grade [3]. Alone, identification characterization somatic DNA alterations insufficient. harbor