Platelet-derived growth factor receptor alpha mutational status and immunohistochemical expression in Merkel cell...

It is not known if Merkel cell carcinomas (MCCs) show mutations in the platelet-derived growth factor receptor alpha (PDGFRA) gene similar to a subset of gastrointestinal stromal cell tumors. The purpose of this study was to analyze MCCs for mutations in the PDGFRA gene as well as to analyze those MCCs exhibiting a possible mutation in the PDGFRA gene for immunohistochemical expression of PDGFRA.

We extracted tumor DNA from nine MCCs, performed polymerase chain reaction amplification of PDGFRA exons 10, 12, 14 and 18, and directly sequenced those gene products for mutations. In addition, we evaluated for PDGFRA immunostaining in three MCCs showing a possible PDGFRA gene mutation.

Three out of nine (33.3%) MCCs showed an identical novel single heterozygous base change in exon 10 of the PDGFRA gene leading to an amino acid substitution at codon 478. In addition, all three (100%) of those MCCs expressed PDGFRA.

Although it is unknown whether the base change described above represents a true mutation or a single nucleotide polymorphism, the fact that this change was absent in our control specimens suggests that this mutation may be oncogenic in nature and may make imatinib mesylate a possible therapeutic option in MCC.