Title |
Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma
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Published in |
Nature Genetics, April 2014
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DOI | 10.1038/ng.2925 |
Pubmed ID | |
Authors |
Kathryn R Taylor, Alan Mackay, Nathalène Truffaux, Yaron S Butterfield, Olena Morozova, Cathy Philippe, David Castel, Catherine S Grasso, Maria Vinci, Diana Carvalho, Angel M Carcaboso, Carmen de Torres, Ofelia Cruz, Jaume Mora, Natacha Entz-Werle, Wendy J Ingram, Michelle Monje, Darren Hargrave, Alex N Bullock, Stéphanie Puget, Stephen Yip, Chris Jones, Jacques Grill |
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 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 22% |
Netherlands | 1 | 11% |
France | 1 | 11% |
Australia | 1 | 11% |
Unknown | 4 | 44% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 4 | 44% |
Scientists | 4 | 44% |
Science communicators (journalists, bloggers, editors) | 1 | 11% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 6 | 2% |
France | 2 | <1% |
Spain | 2 | <1% |
Netherlands | 1 | <1% |
Italy | 1 | <1% |
United Kingdom | 1 | <1% |
Portugal | 1 | <1% |
Japan | 1 | <1% |
Sweden | 1 | <1% |
Other | 0 | 0% |
Unknown | 362 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 69 | 18% |
Researcher | 66 | 17% |
Student > Master | 32 | 8% |
Student > Bachelor | 32 | 8% |
Student > Doctoral Student | 24 | 6% |
Other | 76 | 20% |
Unknown | 79 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 80 | 21% |
Medicine and Dentistry | 73 | 19% |
Agricultural and Biological Sciences | 65 | 17% |
Neuroscience | 20 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 11 | 3% |
Other | 42 | 11% |
Unknown | 87 | 23% |