Gastrointestinal Stromal Tumor With Multiple Primary Tyrosine Kinase Mutations—Clinicopathologic and Molecular Characterization. Issue 6 (July 2019)

• Record Type: Journal Article
• Authors: Wong, Newton A.C.S.; Taniere, Philippe; Walsh, Shaun; Wallace, Andrew; Nonaka, Daisuke; Jones, Thomas; Gonzalez, David
• Is Part Of: Applied immunohistochemistry & molecular morphology. Volume 27:Issue 6(2019)
• Publication Date: 2019-07
• Subjects: GIST -- KIT -- PDGFRA -- mutation -- genetic heterogeneity -- next generation sequencing; Diagnostic immunohistochemistry -- Periodicals; Immunohistochemistry -- Periodicals; Cells -- Morphology -- Periodicals; Molecular diagnosis -- Periodicals; 616.079
• DOI: 10.1097/PAI.0000000000000660
• Languages: English
• ISSNs: 1541-2016

Abstract

Abstract : A unique cohort of chemo-naive gastrointestinal stromal tumors (GISTs) with double-primary tyrosine kinase mutations was characterized particularly to determine whether coexistent mutations represent a single mutational event. Up to 2013, 4 UK centers reported 9 GISTs with 2 primary tyrosine kinase mutations. In each of 8 cases validated by next generation sequencing, both mutations were present in the same allele of the same exon ( KIT exon 11 or 17, or PDGFRA exon 18). One case showed the second mutation only on some of the mutant alleles. Seven cases showed both mutations in all the reads, but in 2 cases, additional variants were found only in some reads. Clinicopathologic features of the 8 cases were similar to GISTs with single-primary mutations. When GIST genotyping rarely uncovers multiple tyrosine kinase variants in an exon, they occur in the same allele but are likely to represent separate mutational events and lack clinical significance.