Diffuse intrinsic pontine gliomas (DIPGs) are highly infiltrative malignant 
glial neoplasms of the ventral pons that, due to their location within the 
brain, are unsuitable for surgical resection and consequently have a universally 
dismal clinical outcome. The median survival time is 9-12 months, with neither 
chemotherapeutic nor targeted agents showing substantial survival benefit in 
clinical trials in children with these tumors. We report the identification of 
recurrent activating mutations in the ACVR1 gene, which encodes a type I activin 
receptor serine/threonine kinase, in 21% of DIPG samples. Strikingly, these 
somatic mutations (encoding p.Arg206His, p.Arg258Gly, p.Gly328Glu, p.Gly328Val, 
p.Gly328Trp and p.Gly356Asp substitutions) have not been reported previously in 
cancer but are identical to mutations found in the germ line of individuals with 
the congenital childhood developmental disorder fibrodysplasia ossificans 
progressiva (FOP) and have been shown to constitutively activate the BMP-TGF-β 
signaling pathway. These mutations represent new targets for therapeutic 
intervention in this otherwise incurable disease.