Faculty Bibliography

Low-grade astrocytomas (LGAs) carry neomorphic mutations in isocitrate dehydrogenase (IDH) concurrently with P53 and ATRX loss. To model LGA formation, we introduced R132H IDH1, P53 shRNA, and ATRX shRNA into human neural stem cells (NSCs). These oncogenic hits blocked NSC differentiation, increased invasiveness in vivo, and led to a DNA methylation and transcriptional profile resembling IDH1 mutant human LGAs. The differentiation block was caused by transcriptional silencing of the transcription factor SOX2 secondary to disassociation of its promoter from a putative enhancer. This occurred because of reduced binding of the chromatin organizer CTCF to its DNA motifs and disrupted chromatin looping. Our human model of IDH mutant LGA formation implicates impaired NSC differentiation because of repression of SOX2 as an early driver of gliomagenesis.

BACKGROUND: Concurrent chemoradiation (CCRT) and upfront surgery followed by adjuvant therapy both are recommended treatment options for patients with advanced stage squamous cell carcinoma (SCC) of the tonsil. To the authors' knowledge, the question of whether surgical-based treatments can achieve better survival compared with CCRT has never been compared in a clinical trial. The authors analyzed the National Cancer Data Base to measure the impact of different treatment modalities on overall survival (OS). METHODS: All patients aged