Diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors for which there is currently no effective treatment. Some of these tumors combine gain-of-function mutations in ACVR1, PIK3CA, and histone H3-encoding genes. The oncogenic mechanisms of action of ACVR1 mutations are currently unknown. Using mouse models, we demonstrate that Acvr1 G328V arrests the differentiation of oligodendroglial lineage cells, and cooperates with Hist1h3b K27M and Pik3ca H1047R to generate high-grade diffuse gliomas. Mechanistically, Acvr1 G328V upregulates transcription factors which control differentiation and DIPG cell fitness. Furthermore, we characterize E6201 as a dual inhibitor of ACVR1 and MEK1/2, and demonstrate its efficacy toward tumor cells in vivo. Collectively, our results describe an oncogenic mechanism of action for ACVR1 mutations, and suggest therapeutic strategies for DIPGs.

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A system for assessing the severity of mucositis in patients undergoing bone marrow transplantation (BMT) is presented. Ten criteria were graded to give component scores together with a total score. The overall severity score ranged from 0 through 21. Scores were assigned three times daily by nursing staff members and verified daily by the attending dental and medical practitioners. Total scores were highly reproducible and were related to the severity of neutropenia. Variation between sequential total scores was not related to interexaminer variation but rather to changes in the severity of oral mucositis. Component scores provided a useful means for transmitting oral health information between health care personnel. Total scores were used to regulate the nature and frequency of oral hygiene procedures for patients undergoing BMT as well as other hematology/oncology patients. Application of this oral assessment system to other institutional settings may be beneficial.

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