Science (New York, N.Y.), 19 December 2014, Vol.346(6216), pp.1458-9
Diffuse intrinsic pontine glioma (DIPG) is an incurable pediatric brain tumor. About 80% of these tumors contain mutations in genes that encode histones (H3.3 or H3.1) ( 1 , 2 ), proteins that package DNA into chromatin. These mutations, which change lysine 27 to methionine (K27M), are believed to sequester Polycomb repressive complex 2 (PRC2), which normally represses gene expression through histone methylation (see the figure). In the absence of PRC2, genes that should be silent are expressed, which is thought to drive cell transformation ( 3 – 5 ). However, the precise role of histone mutations in tumorigenesis is unclear, and strategies to target the mutations remain elusive. As reported by Funato et al. on page 1529 of this issue ( 6 ), as well as by Hashizume et al. ( 7 ), models of K27M-mutant DIPG can be used to elucidate the mechanisms of transformation and to identify new approaches to therapy.
Models, Genetic ; Brain Stem Neoplasms -- Genetics ; Cell Transformation, Neoplastic -- Genetics ; Embryonic Stem Cells -- Metabolism ; Glioma -- Genetics ; Histones -- Genetics ; Neural Stem Cells -- Metabolism
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