Elsevier

Bone

Volume 109, April 2018, Pages 91-100
Bone

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

https://doi.org/10.1016/j.bone.2017.08.001Get rights and content
Under a Creative Commons license
open access

Highlights

  • Fibrodysplasia Ossificans Progressiva (FOP) and Diffuse Intrinsic Pontine Gliomas (DIPGs) share ACVR1 mutations.

  • While ACVR1 mutations underlie FOP, their functional role in DIPG remains unclear.

  • Developmental biology provides a context of shared biology among diverse diseases.

  • Intersecting Mendelian disorders and cancer genomics can elucidate potential cancer genes.

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.

Abbreviations

BMP
bone morphogenetic protein
CNS
central nervous system
DIPG
Diffuse Intrinsic Pontine Glioma
FOP
Fibrodysplasia Ossificans Progressiva
GBM
glioblastoma
GSCs
glioma stem cells
HO
heterotopic ossification
NPCs
neural progenitor cells
OPCs
oligodendrocyte precursor cells
SE
superenhancers

Keywords

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

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1

Present address: Department of Medicine, University of California, San Francisco, 505 Parnassus Ave., Rm. 987, San Francisco, CA 94143-0119, United States of America.