Diffuse midline gliomas (DMGs) are universally fatal childhood brain tumors with a median survival of <1 year1,2. The majority (~80%) of these tumors harbor a somatic, heterozygous mutation in H3-3A (denoted H3F3A herein) or H3C2 (also known as HIST1H3B) (genes that encode histone H3 proteins), resulting in a lysine-to-methionine substitution at position 27 (K27M)3,4. The most common mutations occur in H3F3A, which encodes the histone H3 variant H3.3.

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