Overexpression and amplification of alpha-PDGF receptor gene lacking exons coding for a portion of the extracellular region in a malignant glioma.

Overexpression of the alpha-Platelet Derived Growth Factor Receptor (alpha-PDGF) gene was detected in a case of malignant glioma. This overexpression was accompanied with amplification of rearranged alpha-PDGF receptor gene. We have isolated a cDNA for the transcript derived from the amplified receptor gene. Characterization of the cDNA revealed a deletion of 243 nucleotides coding for 81 amino acids in the extracellular region of the receptor. This in-frame deletion removed a part of the immunoglobulin-like domains in the extracellular region of the receptor. Analysis of the amplified alpha-PDGF receptor gene in the glioma indicated that exons coding for the 81 amino acids were lost by a gene deletion. The gene amplification was also detected in macroscopically normal cortex adjacent to the glioma from the same patient. However, the amplified gene in the macroscopically normal cortex had no major gene rearrangement. These data suggest that the overproduction of structurally altered alpha-PDGF receptor may take part in the onset and the development of malignant glioma.