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Bone. 2018 Apr;109:91-100. doi: 10.1016/j.bone.2017.08.001. Epub 2017 Aug 2.

Shared ACVR1 mutations in FOP and DIPG: Opportunities and challenges in extending biological and clinical implications across rare diseases.

Author information

1
Division of Neurosurgery, The Children's Hospital of Philadelphia, Colket Translational Research Building Room 4052, 3501 Civic Center Blvd, Philadelphia 19104, PA, United States; Department of Neurosurgery, Perelman School of Medicine at the University of Pennsylvania, 3501 Civic Center Blvd, Room 4052, Philadelphia 19104, PA, United States.
2
Division of Neurosurgery, The Children's Hospital of Philadelphia, Colket Translational Research Building Room 4052, 3501 Civic Center Blvd, Philadelphia 19104, PA, United States; Center for Data Driven Discovery in Biomedicine, The Children's Hospital of Philadelphia, Colket Translational Research Building Room 4052, 3501 Civic Center Blvd, Philadelphia 19104, PA, United States; Department of Neurosurgery, Perelman School of Medicine at the University of Pennsylvania, 3501 Civic Center Blvd, Room 4052, Philadelphia 19104, PA, United States.
3
Division of Neurosurgery, The Children's Hospital of Philadelphia, Colket Translational Research Building Room 4052, 3501 Civic Center Blvd, Philadelphia 19104, PA, United States; Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, Colket Translational Research Building Room 4052, 3501 Civic Center Blvd, Philadelphia 19104, PA, United States; Center for Data Driven Discovery in Biomedicine, The Children's Hospital of Philadelphia, Colket Translational Research Building Room 4052, 3501 Civic Center Blvd, Philadelphia 19104, PA, United States; Center for Childhood Cancer Research, The Children's Hospital of Philadelphia, Colket Translational Research Building Room 4052, 3501 Civic Center Blvd, Philadelphia 19104, PA, United States; Department of Neurosurgery, Perelman School of Medicine at the University of Pennsylvania, 3501 Civic Center Blvd, Room 4052, Philadelphia 19104, PA, United States. Electronic address: resnick@email.chop.edu.

Abstract

Gain-of-function mutations in the Type I Bone Morphogenic Protein (BMP) receptor ACVR1 have been identified in two diseases: Fibrodysplasia Ossificans Progressiva (FOP), a rare autosomal dominant disorder characterized by genetically driven heterotopic ossification, and in 20-25% of Diffuse Intrinsic Pontine Gliomas (DIPGs), a pediatric brain tumor with no effective therapies and dismal median survival. While the ACVR1 mutation is causal for FOP, its role in DIPG tumor biology remains under active investigation. Here, we discuss cross-fertilization between the FOP and DIPG fields, focusing on the biological mechanisms and principles gleaned from FOP that can be applied to DIPG biology. We highlight our current knowledge of ACVR1 in both diseases, and then describe the growing opportunities and barriers to effectively investigate ACVR1 in DIPG. Importantly, learning from other seemingly unrelated diseases harboring similar mutations may uncover novel mechanisms or processes for future investigation.

KEYWORDS:

ACVR1; BMP; Childhood cancers; Diffuse Intrinsic Pontine Glioma; Fibrodysplasia Ossificans Progressiva; Mendelian disorders

PMID:
28780023
DOI:
10.1016/j.bone.2017.08.001
[Indexed for MEDLINE]
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