PerspectiveCANCER

For pediatric glioma, leave no histone unturned

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Science  19 Dec 2014:
Vol. 346, Issue 6216, pp. 1458-1459
DOI: 10.1126/science.aaa3814

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Summary

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 (35). 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.