Taylor, KR;
Mackay, A;
Truffaux, N;
Butterfield, YS;
Morozova, O;
Philippe, C;
Castel, D;
... Grill, J; + view all
(2014)
Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma.
Nature Genetics
, 46
(5)
pp. 457-461.
10.1038/ng.2925.
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Abstract
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 tumors1. 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)2 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.
| Type: | Article |
|---|---|
| Title: | Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ng.2925 |
| Publisher version: | https://doi.org/10.1038/ng.2925 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | DIPG; ACVR1; ALK2; Fibrodysplasia ossificans progressiva; BMP/TGF-β |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1431055 |
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