Penttinen syndrome-associated PDGFRB Val665Ala variant causes aberrant constitutive STAT1 signalling.

Penttinen syndrome is a rare progeroid disorder caused by mutations in platelet-derived growth factor (PDGF) receptor beta (encoded by the PDGFRB proto-oncogene) and characterized by a prematurely aged appearance with lipoatrophy, skin lesions, thin hair and acro-osteolysis. Activating mutations in PDGFRB have been associated with other human diseases, including Kosaki overgrowth syndrome, infantile myofibromatosis, fusiform aneurysms, acute lymphoblastic leukaemia and myeloproliferative neoplasms associated with eosinophilia. The goal of the present study was to characterize the PDGFRB p.

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.

miR-223 potentially targets SWI/SNF complex protein SMARCD1 in atypical proliferative serous tumor and high-grade ovarian serous carcinoma.

Ovarian cancer is the fifth most common cancer in women worldwide and has the highest mortality amongst gynecological cancers. miRNAs are a class of non-coding RNAs, approximately 22 nt long, that negatively regulate gene expression and have roles in cell growth, differentiation, metabolism, apoptosis and tumorigenesis. Dysregulated miRNA-223 expression has been implicated in a wide range of cancer subtypes.

A patient with germ-line gain-of-function PDGFRB p.N666H mutation and marked clinical response to imatinib.

PurposeHeterozygous germ-line activating mutations in PDGFRB cause Kosaki and Penttinen syndromes and myofibromatosis. We describe a 10-year-old child with a germ-line PDGFRB p.N666H mutation who responded to the tyrosine kinase inhibitor imatinib by inhibition of PDGFRB.

PDGFRB gain-of-function mutations in sporadic infantile myofibromatosis.

Infantile myofibromatosis is one of the most prevalent soft tissue tumors of infancy and childhood. Multifocal nodules with visceral lesions are associated with a poor prognosis. A few familial cases have been linked to mutations in various genes including PDGFRB.

Idiopathic basal ganglia calcification-associated PDGFRB mutations impair the receptor signalling.

Platelet-derived growth factors (PDGF) bind to two related receptor tyrosine kinases, which are encoded by the PDGFRA and PDGFRB genes. Recently, heterozygous PDGFRB mutations have been described in patients diagnosed with idiopathic basal ganglia calcification (IBGC or Fahr disease), a rare inherited neurological disorder. The goal of the present study was to determine whether these mutations had a positive or negative impact on the PDGFRB activity.

The tyrosine phosphatase SHP2 is required for cell transformation by the receptor tyrosine kinase mutants FIP1L1-PDGFRα and PDGFRα D842V.

Activated forms of the platelet derived growth factor receptor alpha (PDGFRα) have been described in various tumors, including FIP1L1-PDGFRα in patients with myeloproliferative diseases associated with hypereosinophilia and the PDGFRα(D842V) mutant in gastrointestinal stromal tumors and inflammatory fibroid polyps. To gain a better insight into the signal transduction mechanisms of PDGFRα oncogenes, we mutated twelve potentially phosphorylated tyrosine residues of FIP1L1-PDGFRα and identified three mutations that affected cell proliferation. In particular, mutation of tyrosine 720 in FIP1L1-PDGFRα or PDGFRα(D842V) inhibited cell growth and blocked ERK signaling in Ba/F3 cells.