Gastrointestinal Stromal Tumor With Multiple Primary Tyrosine Kinase Mutations—Clinicopathologic and Molecular Characterization

摘要

It is current dogma that a gastrointestinal stromal tumor (GIST) which has not been treated with a tyrosine kinase inhibitor (TKI)—that is, a chemo-naive GIST—harbors only one primary TK {KIT or PDGFRA) mutation.1'2 The latter term is traditionally used to distinguish from acquired or so-called secondary TK mutations which are induced by TKI therapy.1'2 Despite this dogma, there have been rare reports of chemo-naive GISTs with double-primary TK mutations. These reports have included variable genetic data and generally limited clinicopathologic details. These reported cases have never described the coexisting mutations to occur in different genes. The double-primary mutant GIST reported by Heinrich et al harbored a mutation each in KIT exons 13 and 17.3 A more recent case similarly described coexisting KIT exon 11 and exon 17 mutations, though there was no clarification whether the GIST was chemo-naive.4 All the other reported cases described double-primary mutations in the same exon of the same gene. For example, among 135 small (<2cm diameter) GISTs, 4 harbored double-primary mutations: 2 with KIT exon 9 mutations, 1 with KIT exon 11 mutations, and 1 with PDGFRA exon 18 mutations.5 More recently, Conca et al6 described a GIST with double-primary mutations in KIT exon 11.