Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

Genetics

ACVR1 mutations—a key piece in paediatric diffuse glioma

Nature Reviews Clinical Oncology volume 11, page 300 (2014)Cite this article

Subjects

High-grade glioma—or high-grade astrocytoma (HGA)—have a devastating prognosis, with survival ranging from 20–30% for tumours outside the brainstem, and less than 10% for diffuse intrinsic pontine gliomas (DIPGs), which arise in the brainstem and are found almost exclusively in children. Aside from radiotherapy, there is currently no effective treatment for this type of cancer, and most children will die of their tumours within 1–2 years of diagnosis. This lack of effective treatment could be due to the fact that drug development in this field has been designed based on the biology of adult glioma when, in fact, the spectrum of molecular alterations in children is very different. Now, four independent papers published in Nature Genetics have identified mutations in the gene ACVR1 in patients with DIPG, revealing a crucial role of this gene in the development of this type of brain tumour. The ACVR1 gene encodes for the activin receptor type I protein, which is a receptor of the bone morphogenetic proteins (BMPs). None of these mutations had previously been found in cancer, although they are linked to an inherited muscular disease known as fibrodysplasia ossificans progressiva.

In turn, Baker and colleagues sequenced 127 tumour–normal pairs of HGA samples (DIPGs and other paediatric HGA that arise outside the brainstem) from 118 patients. “We also completed whole-genome or whole-exome sequencing on the matched germline DNA for 108 of these cases so that we could identify all somatic mutations,” explains Baker. The authors reported recurrent somatic mutations in ACVR1 exclusively in DIPGs, in 32% of the samples.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

References

  1. Wu, G. et al. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat. Genet. 46, 444–450 (2014)

    Article  CAS  Google Scholar 

  2. Buczkowicz, P. et al. Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nat. Genet. 46, 451–456 (2014)

    Article  CAS  Google Scholar 

  3. Taylor, K. R. et al. Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. Nat. Genet. 46, 457–461 (2014)

    Article  CAS  Google Scholar 

  4. Fontebasso, A. M. et al. Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma. Nat. Genet. 46, 462–466 (2014)

    Article  CAS  Google Scholar 

Download references

Authors
  1. M. Teresa Villanueva
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Villanueva, M. ACVR1 mutations—a key piece in paediatric diffuse glioma. Nat Rev Clin Oncol 11, 300 (2014). https://doi.org/10.1038/nrclinonc.2014.74

Download citation

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/nrclinonc.2014.74

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer