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Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation

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Science  19 Dec 2014:
Vol. 346, Issue 6216, pp. 1529-1533
DOI: 10.1126/science.1253799

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Modeling brain cancer from stem to stern

Diffuse intrinsic pontine gliomas (DIPGs) are aggressive brain tumors primarily affecting children. Because the tumors arise in the brainstem, which controls many vital functions, they cannot be surgically excised and are often fatal. To study the pathogenesis of DIPGs—in particular, the role of a histone H3.3 mutation that occurs in 70% of cases—Funato et al. developed a new tumor model (see the Perspective by Becher and Wechsler-Reya). They first directed the differentiation of embryonic stem cells into neural progenitor cells. They then introduced a specific combination of genes, including the mutant histone gene, and found that this caused the progenitor cells to acquire features characteristic of cancer cells. During this oncogenic transformation, the cells reverted to a more primitive differentiation state and displayed altered histone marks at several key regulatory genes.

Science, this issue p. 1529; see also p. 1458