PDGF receptor mutations in human diseases


PDGFRA and PDGFRB are classical proto-oncogenes that encode receptor tyrosine kinases responding to platelet-derived growth factor (PDGF). PDGFRA mutations are found in gastrointestinal stromal tumors (GISTs), inflammatory fibroid polyps and gliomas, and PDGFRB mutations drive myofibroma development. In addition, chromosomal rearrangement of either gene causes myeloid neoplasms associated with hypereosinophilia. Recently, mutations in PDGFRB were linked to several noncancerous diseases. Germline heterozygous variants that reduce receptor activity have been identified in primary familial brain calcification, whereas gain-of-function mutants are present in patients with fusiform aneurysms, Kosaki overgrowth syndrome or Penttinen premature aging syndrome. Functional analysis of these variants has led to the preclinical validation of tyrosine kinase inhibitors targeting PDGF receptors, such as imatinib, as a treatment for some of these conditions. This review summarizes the rapidly expanding knowledge in this field.

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The authors were supported by grants from the Foundation against Cancer and King-Baudouin Foundation (Belgium). E.G., F.A. and G.D. are recipients of fellowships from National Fund for Scientific Research (FNRS) (Belgium).

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EG, FA, GD, BB and JBD wrote the manuscript. EG drew the figures.

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Correspondence to Jean-Baptiste Demoulin.

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Guérit, E., Arts, F., Dachy, G. et al. PDGF receptor mutations in human diseases. Cell. Mol. Life Sci. (2021). https://doi.org/10.1007/s00018-020-03753-y

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