Gastrointestinal stromal tumors (GISTs): point mutations matter in management, a review

Abstract

The therapeutic implications of the genomic alterations seen within the drivers of gastrointestinal stromal tumors (GIST) are among the best understood in all of solid tumors. Sequencing of cKIT and PDGFRα should be considered standard practice for the treatment of GIST patients. In this article, we will review the common mutations and how they are utilized in clinical management. In addition, we will review the rare D842V PDGFRα mutation and the diverse molecular group that lacks a mutation in either cKIT or PDGFRα (wild-type GIST) which are best treated on clinical trial. Finally, we will look forward at the future therapies that are ever evolving for management of GIST. Taken together, the scientific advances in understanding the molecular basis of GIST validates the importance of knowing and understanding the mutations that are present in any one patient.

Keywords: Gastrointestinal stromal tumors (GIST); PDGFRa; cKIT; wild type GIST.

Figure 1

Cartoon representing the distribution of point mutations in cKIT and PDGFRa by exon. While most mutations occur in exon 11 of cKIT (70%), others commonly occur in cKIT at exons 9, 13, 14 and 17 and in PDGFRa at exons 12 and 18.