PT  - JOURNAL ARTICLE
AU  - Newton A C S Wong
AU  - Olivier T Giger
AU  - Rogier ten Hoopen
AU  - Ruth T Casey
AU  - Kirsty Russell
AU  - Claire Faulkner
TI  - Next-generation sequencing demonstrates the rarity of short kinase variants specific to quadruple wild-type gastrointestinal stromal tumours
AID  - 10.1136/jclinpath-2020-206613
DP  - 2021 Mar 01
TA  - Journal of Clinical Pathology
PG  - 194--197
VI  - 74
IP  - 3
4099  - http://jcp.bmj.com/content/74/3/194.short
4100  - http://jcp.bmj.com/content/74/3/194.full
SO  - J Clin Pathol2021 Mar 01; 74
AB  - Aim There is no known specific biomarker or genetic signal for quadruple wild-type (qWT) gastrointestinal stromal tumours (GISTs). By next-generation sequencing (NGS) of different GIST subgroups, this study aimed to characterise such a biomarker especially as a potential therapeutic target.Methods and results An NGS panel of 672 kinase genes was applied to DNA extracted from 11 wild-type GISTs (including three qWT GISTs) and 5 KIT/PDGFRA mutated GISTs. Short variants which were present in qWT GISTs but no other GIST subgroup were shortlisted. After removing common population variants, in silico-classified deleterious variants were found in CSNK2A1, MERTK, RHEB, ROCK1, PIKFYVE and TRRAP. None of these variants were demonstrated in a separate cohort of four qWT GISTs.Conclusions Short kinase variants which are specific to qWT GISTs are rare and are not universally demonstrated by this whole subgroup. It is therefore possible that the current definition of qWT GIST still covers a heterogenous population.