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

TY - JOUR

T1 - Gastrointestinal Stromal Tumor With Multiple Primary Tyrosine Kinase Mutations-Clinicopathologic and Molecular Characterization

AU - Wong, Newton A. C. S.

AU - Taniere, Philippe

AU - Walsh, Shaun

AU - Wallace, Andrew

AU - Nonaka, Daisuke

AU - Jones, Thomas

AU - Gonzalez, David

PY - 2019/7

Y1 - 2019/7

N2 - 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.

AB - 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.

U2 - 10.1097/PAI.0000000000000660

DO - 10.1097/PAI.0000000000000660

M3 - Article

C2 - 29734250

SN - 1541-2016

VL - 27

SP - 461

EP - 465

JO - Applied Immunohistochemistry and Molecular Morphology

JF - Applied Immunohistochemistry and Molecular Morphology

IS - 6

ER -