Recurrent Activating ACVR1 Mutations in Diffuse Intrinsic Pontine Glioma

Overview

Journal Nat Genet

Specialty Genetics

Date 2014 Apr 8

PMID 24705252

Citations 278

Authors

Kathryn R Taylor

Alan Mackay

Nathalene Truffaux

Yaron 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

Stephanie Puget

Stephen Yip

Chris Jones

Jacques Grill

Affiliations

Soon will be listed here.

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.

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