Gene

PDGFRB

Biology

PDGFB

Growth factor

Stromal cell

Platelet-derived growth factor receptor

Receptor

GiST

Receptor tyrosine kinase

Cancer research

Growth factor receptor

Immunology

Myeloid leukemia

Hypereosinophilia

Genetics

Receptor Protein-Tyrosine Kinases

Imatinib

Tyrosine kinase

PDGFRA

Eosinophilia

Cellular and Molecular Life Sciences

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.

PDGF receptor mutations in human diseases