Patient-derived Tumor Models for Diffuse Intrinsic Pontine Gliomas
CURRENT NEUROPHARMACOLOGY
Authors: Hashizume, Rintaro; Gupta, Nalin
Abstract
Background: Diffuse intrinsic pontine gliomas represent a unique subtype of primary brain tumors occuring in a specific location and age. Their growth demonstrates early invasion and, following diagnosis, rapid growth not responsive to common therapies. Until recently, the genetic and cellular basis of these tumors was unknown. Genetic evidence implicates mutations in the histone genes in the origin of these tumors. Methods: Surgical biopsies performed on selected patients have resulted in the establishment of anatomically accurate mouse models that have been used to examine patterns of growth and response to new therapeutic agents. Results: Human derived pontine glioma models recapitulate the invasive patterns of growth. The grade of the original tumor affects the latency of tumor growth after implantation. Conclusion: The use of human-derived xenograft models allows for improved pre-clinical testing of new therapeutic targets in a tumor-and organ-specific manner.
A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva
NATURE GENETICS
Authors: Shore, EM; Xu, MQ; Feldman, GJ; Fenstermacher, DA; Brown, MA; Kaplan, FS
Abstract
Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. We mapped FOP to chromosome 2q23-24 by linkage analysis and identified an identical heterozygous mutation (617G -> A; R206H) in the glycine-serine (GS) activation domain of ACVR1, a BMP type I receptor, in all affected individuals examined. Protein modeling predicts destabilization of the GS domain, consistent with constitutive activation of ACVR1 as the underlying cause of the ectopic chondrogenesis, osteogenesis and joint fusions seen in FOP.
COA
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