Ultrastructural features and platelet-derived growth factor receptor A gene mutations in CD117-negative gastrointestinal stromal tumor

Abstract

To explore the ultrastructural features and mutation status of platelet-derived growth factor receptors A (PDGFRA) and c-kit in gastrointestinal stromal tumors that were immunohistochemically negative for CD117 antigen. Six cases of gastrointestinal stromal tumors that were CD117 immunostain negative were studied by electron microscopy. Direct PCR sequencing was used to investigate the mutation status of c-kit gene exons 9, 11, 13, 17 and PDGFRA gene exons 12 and 18. The ultrastructural features of all 6 cases were similar to those of the interstitial cell of Cajal (ICC). None of the 6 cases were found to have c-kit gene mutations. However, three tumors were found to harbor PDGFRA exon 18 activating mutations, including two tumors having an Asp-->Val842 missense mutation and one having an Arg-->Ser841 missense mutation. PDGFRA mutations may provide an important alternative molecular mechanism for the development of gastrointestinal stromal tumor.