• Home
  • Search Results
  • PDGFRA alterations in cancer: characterization of a gain-of-function V536E transmembrane mutant as well as loss-of-function and passenger mutations.

PDGFRA alterations in cancer: characterization of a gain-of-function V536E transmembrane mutant as well as loss-of-function and passenger mutations.

Oncogene (2013-06-12)
A I Velghe, S Van Cauwenberghe, A A Polyansky, D Chand, C P Montano-Almendras, S Charni, B Hallberg, A Essaghir, J-B Demoulin
ABSTRACT

Activating mutations in the platelet-derived growth factor (PDGF) receptor alpha (PDGFRA) have been described in patients with gastrointestinal stromal tumors or myeloid malignancies associated with hypereosinophilia. These patients respond well to imatinib mesylate, raising the question as to whether patients with a PDGF receptor mutation in other tumor types should receive a tyrosine kinase inhibitor treatment. We characterized 10 novel somatic point mutations in PDGFRA that have been reported in isolated cases of glioblastoma, melanoma, acute myeloid leukemia, peripheral nerve sheath tumors and neuroendocrine carcinoma. The PDGFRA transmembrane domain mutation V536E stimulated Ba/F3 cell growth and signaling via ERK and STAT5 in the absence of ligand. This mutant, identified in glioblastoma, was strongly inhibited by imatinib. Modeling suggested that the mutation modulates the packing of the transmembrane domain helices in the receptor dimer. By contrast, two mutations in highly conserved residues affected the receptor traffic to the cell surface or kinase activity, thereby preventing the response to PDGF. The other mutations had no significant impact on the receptor activity. This functional analysis matched the predictions of SIFT and PolyPhen for only five mutations and these algorithms do not discriminate gain from loss of function. Finally, an E996K variant that had been identified in a melanoma cell line was not expressed in these cells. Altogether, several newly identified PDGFRA mutations do not activate the receptor and may therefore represent passenger mutations. Our results also underline the importance of characterizing novel kinase alterations in cancer patients.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-AKT antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-phospho-AKT1 (pSer473) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-phospho-Akt (pSer473) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-phospho-Akt (pThr308) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-phospho-MNK1 (pThr255) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-phospho-AKT1 (pThr308) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-phospho-Mnk1 (pThr385) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-phospho-Akt1 (pThr450) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-phospho-Akt (pSer124) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-phospho-Akt (pTyr474) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-phospho-Akt (pSer129) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-phospho-Akt (pThr72) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT1 antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-Akt1 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-phospho-MAPK3 (pThr202) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-phospho-MAPK3 (pTyr204) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-phospho-AKT1 (pThr450) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT1 (Ab-473) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT1 (Ab-450) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT1 (Ab-308) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-phospho-AKT1 (pThr308) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Monoclonal Anti-AKT1 antibody produced in mouse, clone 6D6, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-AKT1 antibody produced in mouse, clone 2H1, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-AKT1 antibody produced in mouse, clone 4B9, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-AKT1 antibody produced in mouse, clone 6G6, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-AKT1 antibody produced in rabbit, affinity isolated antibody