Table 2.

Wild-type GIST molecular sub-groupings and treatment.

Molecular alteration	Features	Systemic treatment
SDH-deficient	Germline (Carney Stratakis Syndrome) 47 or sporadic47–49 (can be associated with Carney Triad) 7.5%–12% of GISTs 50 (80% of wild-type GISTs) The most common type of GIST in adolescents and young adults (AYA) Rare in older adults Often young women	Sunitinib 51 Regorafenib 52 Preliminary results with temozolomide 53
NF1-associated	Classical physical findings of NF1 10% of GISTs 54	Local therapy Selumetinib
BRAF mutant 55	3%–4% of GISTs 54 Most common mutation p.V600E 56	BRAF Inhibitor (Dabrafenib, Vemurafenib) 57 BRAF + MEK Inhibitor (Dabrafenib + Trametinib, 58 Vemurafenib + Cobimetinib)
NTRK fusion 59	Very rare Incidence in NTRK trials 2%–5%	Entrectinib 60 Larotrectinib 61
FGFR fusion	<2% of GISTs54,62	FGFR inhibitor (i.e. Pemigatinib) 63
No identified molecular alteration		Imatinib Sunitinib Ripretinib Regorafenib 52
No mutation		Imatinib

BRAF + MEK inhibitors, rapidly accelerated fibrosarcoma B-type and mitogen-activated extracellular signal-regulated kinase inhibitors; FGFR, fibroblast growth factor receptor; GIST, gastrointestinal stromal tumour; NF, neurofibromatosis; NTRK, neurotropic receptor tyrosine kinase; SDH, succinate dehydrogenase.