Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma

Taylor, Kathryn R., Mackay, Alan, Truffaux, Nathalene, Butterfield, Yaron S., Morozova, Olena, Philippe, Cathy, Castel, David, Grasso, Catherine S., Vinci, Maria, Carvalho, Diana, Carcaboso, Angel M., De Torres, Carmen, Cruz, Ofelia, Mora, Jaume, Entz-Werle, Natacha, Ingram, Wendy J., Monje, Michelle, Hargrave, Darren, Bullock, Alex N., Puget, Stephanie, Yip, Stephen, Jones, Chris and Grill, Jacques (2014) Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. Nature Genetics, 46 5: 457-461. doi:10.1038/ng.2925

Author Taylor, Kathryn R.
Mackay, Alan
Truffaux, Nathalene
Butterfield, Yaron S.
Morozova, Olena
Philippe, Cathy
Castel, David
Grasso, Catherine S.
Vinci, Maria
Carvalho, Diana
Carcaboso, Angel M.
De Torres, Carmen
Cruz, Ofelia
Mora, Jaume
Entz-Werle, Natacha
Ingram, Wendy J.
Monje, Michelle
Hargrave, Darren
Bullock, Alex N.
Puget, Stephanie
Yip, Stephen
Jones, Chris
Grill, Jacques
Title Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1471-0056
Publication date 2014-01-01
Year available 2014
Sub-type Article (original research)
DOI 10.1038/ng.2925
Open Access Status Not yet assessed
Volume 46
Issue 5
Start page 457
End page 461
Total pages 5
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
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-Î 2 signaling pathway. These mutations represent new targets for therapeutic intervention in this otherwise incurable disease.
Keyword DIPG
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 092809/Z/10/Z
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Queensland Children's Medical Research Institute Publications
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