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Integrating RNA sequencing into neuro-oncology practice

      Malignant tumors of the central nervous system (CNS) cause substantial morbidity and mortality, yet efforts to optimize chemo- and radiotherapy have largely failed to improve dismal prognoses. Over the past decade, RNA sequencing (RNA-seq) has emerged as a powerful tool to comprehensively characterize the transcriptome of CNS tumor cells in one high-throughput step, leading to improved understanding of CNS tumor biology and suggesting new routes for targeted therapies. RNA-seq has been instrumental in improving the diagnostic classification of brain tumors, characterizing oncogenic fusion genes, and shedding light on intratumor heterogeneity. Currently, RNA-seq is beginning to be incorporated into regular neuro-oncology practice in the form of precision neuro-oncology programs, which use information from tumor sequencing to guide implementation of personalized targeted therapies. These programs show great promise in improving patient outcomes for tumors where single agent trials have been ineffective. As RNA-seq is a relatively new technique, many further applications yielding new advances in CNS tumor research and management are expected in the coming years.

      Abbreviations:

      CNS (central nervous system), RNA-seq (RNA sequencing), qRT-PCR (quantitative reverse transcription polymerase chain reaction), NGS (next-generation sequencing), GBM (glioblastoma), SNPs (single nucleotide polymorphisms), exRNAs (extracellular RNAs), lncRNAs (long noncoding RNAs), miRNAs (microRNAs), CNS-PNET (primitive neuroectodermal tumors of the CNS), CNS NB-FOXR2 (CNS neuroblastoma with FOXR2 activation), CNS EFT-CIC (CNS Ewing sarcoma family tumor with CIC alteration), CNS HGNET-MN1 (CNS high-grade neuroepithelial tumor with MN1 alteration), CNS HGNET-BCOR (CNS high-grade neuroepithelial tumor with BCOR alteration), ATRT (atypical teratoid rhabdoid tumors), CIMP (CpG island methylator phenotype), RTK (receptor tyrosine kinase), ADME (absorption, distribution, metabolism and excretion), GSEA (Gene Set Enrichment Analysis), ssGSEA (single-sample Gene Set Enrichment Analysis), IGSA (Individual Gene Sets Analysis), CSC (cancer stem cells)
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