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Abstract: New discoveries in Glioblastoma (GBM) biology have been made using genomics data.  Genomic markers are routinely integrated into clinical neurosurgical practice.  In this manuscript, we review fundamentals of genomics such as the differences between first, second, and third generation sequencing technology.  We also review the impact of single cell genomics in understanding the complex heterogenous GBM microenvironment.  Finally, we will discuss advances in epigenetics that have lent insights into treatment resistance. The integration of genomics into neuro-oncology clinical practice is routine and will continue to expand with the expansion of precision of medicine.  We provide a primer for clinicians.