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Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. | LitMetric

AI Article Synopsis

  • - Diffuse intrinsic pontine gliomas (DIPGs) are aggressive brain tumors located in the ventral pons that are inoperable and have a poor prognosis, with a median survival of only 9-12 months.
  • - Recent research found that 21% of DIPG samples have recurrent mutations in the ACVR1 gene, which are similar to mutations seen in a rare developmental disorder, fibrodysplasia ossificans progressiva (FOP).
  • - These ACVR1 mutations activate specific signaling pathways and may offer new targets for developing treatments for patients with DIPG, a previously untreatable condition.

Article 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018681PMC
http://dx.doi.org/10.1038/ng.2925DOI Listing

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