Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brainstem tumor with a peak incidence in middle childhood and a median survival of less than 1 year. The dismal prognosis associated with DIPG has been exacerbated by the failure of over 250 clinical trials to meaningfully improve survival compared with radiotherapy, the current standard of care. The traditional practice to not biopsy DIPG led to a scarcity in available tissue samples for laboratory analysis that till recently hindered therapeutic advances. Over the past few years, the acquisition of patient derived tumor samples through biopsy and autopsy protocols has led to distinct breakthroughs in the identification of key oncogenic drivers implicated in DIPG development. Aberrations have been discovered in critical genetic drivers including histone H3, ACVR1, TP53, PDGFRA, and Myc. Mutations, previously not identified in other malignancies, highlight DIPG as a distinct biological entity. Identification of novel markers has already greatly influenced the direction of preclinical investigations and offers the exciting possibility of establishing biologically targeted therapies. This review will outline the current knowledge of the genomic landscape related to DIPG, overview preclinical investigations, and reflect how biological advances have influenced the focus of clinical trials toward targeted therapies.

NEURO-ONCOLOGY • JUNE 2017chemotherapy -and observation only. The parents elected careful follow-up. Now 16 months following biopsy, the child is developing well and the MRI is stable, with advanced imaging characteristics of a low-grade glial lesion. Case 2. A male was diagnosed in utero with hydrocephalus, a post-natal MRI confirming this and revealing a small tectal mass. An ETV and biopsy were performed, yielding a tiny tumor fragment; pathology was consistent with a diffuse glial tumor, with rare mitoses; IDH1 and ATRX intact, P53 negative, GFAP positive and Ki67 20-30%. The tumor was deemed a highgrade glioma. Insufficient tissue for sequencing was available. The infant has been followed with close follow-up MRI scans with advanced imaging, which remain consistent with a low-grade glioma, and continues stable at 3 months since birth; a repeat biopsy is planned concomitant with shunt revision. CONCLUSION: Infants with tectal gliomas are rare, and anecdotally never undergo progression to high-grade. In the absence of definitive sequencing data, extreme caution should be exercised in offering treatment recommendations.