% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Fontebasso:120027,
      author       = {A. M. Fontebasso and S. Papillon-Cavanagh and J.
                      Schwartzentruber and H. Nikbakht and N. Gerges and P.-O.
                      Fiset and D. Bechet and D. Faury and N. De Jay and L. A.
                      Ramkissoon and A. Corcoran and D. Jones$^*$ and D. Sturm$^*$
                      and P. Johann$^*$ and T. Tomita and S. Goldman and M. Nagib
                      and A. Bendel and L. Goumnerova and D. C. Bowers and J. R.
                      Leonard and J. B. Rubin and T. Alden and S. Browd and J. R.
                      Geyer and S. Leary and G. Jallo and K. Cohen and N. Gupta
                      and M. D. Prados and A.-S. Carret and B. Ellezam and L.
                      Crevier and A. Klekner and L. Bognar and P. Hauser and M.
                      Garami and J. Myseros and Z. Dong and P. M. Siegel and H.
                      Malkin and A. H. Ligon and S. Albrecht and S. Pfister$^*$
                      and K. L. Ligon and J. Majewski and N. Jabado and M. W.
                      Kieran},
      title        = {{R}ecurrent somatic mutations in {ACVR}1 in pediatric
                      midline high-grade astrocytoma.},
      journal      = {Nature genetics},
      volume       = {46},
      number       = {5},
      issn         = {1546-1718},
      address      = {New York, NY},
      publisher    = {Nature America},
      reportid     = {DKFZ-2017-00615},
      pages        = {462 - 466},
      year         = {2014},
      abstract     = {Pediatric midline high-grade astrocytomas (mHGAs) are
                      incurable with few treatment targets identified. Most tumors
                      harbor mutations encoding p.Lys27Met in histone H3 variants.
                      In 40 treatment-naive mHGAs, 39 analyzed by whole-exome
                      sequencing, we find additional somatic mutations specific to
                      tumor location. Gain-of-function mutations in ACVR1 occur in
                      tumors of the pons in conjunction with histone H3.1
                      p.Lys27Met substitution, whereas FGFR1 mutations or fusions
                      occur in thalamic tumors associated with histone H3.3
                      p.Lys27Met substitution. Hyperactivation of the bone
                      morphogenetic protein (BMP)-ACVR1 developmental pathway in
                      mHGAs harboring ACVR1 mutations led to increased levels of
                      phosphorylated SMAD1, SMAD5 and SMAD8 and upregulation of
                      BMP downstream early-response genes in tumor cells. Global
                      DNA methylation profiles were significantly associated with
                      the p.Lys27Met alteration, regardless of the mutant histone
                      H3 variant and irrespective of tumor location, supporting
                      the role of this substitution in driving the epigenetic
                      phenotype. This work considerably expands the number of
                      potential treatment targets and further justifies
                      pretreatment biopsy in pediatric mHGA as a means to orient
                      therapeutic efforts in this disease.},
      keywords     = {Bone Morphogenetic Proteins (NLM Chemicals) / Smad Proteins
                      (NLM Chemicals) / ACVR1 protein, human (NLM Chemicals) /
                      Activin Receptors, Type I (NLM Chemicals)},
      cin          = {B062},
      ddc          = {570},
      cid          = {I:(DE-He78)B062-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:24705250},
      pmc          = {pmc:PMC4282994},
      doi          = {10.1038/ng.2950},
      url          = {https://inrepo02.dkfz.de/record/120027},
}