A patient’s genotype is significantly associated with the risk of gastrointestinal stromal tumor (GIST) recurrence, according to a new study published in the Annals of Gastroenterological Surgery. Analyzing a patient’s genotype can therefore help predict disease prognosis and the best treatment approach. 

The role of genotypes in the prognosis of GISTs has been controversial. Here, a team of researchers led by Seiichi Hirota, MD, PhD, from the Department of Surgical Pathology at Hyogo College of Medicine in Nishinomiya, Japan analyzed data on 402 patients with GISTs who underwent surgery to treat the tumors but received no adjuvant therapy.

The researchers looked at the type and locations of KIT and platelet-derived growth factor receptor alfa (PDGFRA) mutations, as most GISTs harbor a mutation in one of these 2 genes. The team then examined the association between the genotypic characteristics of the patients and their disease prognosis.

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They found that mutations in the KIT gene had broad malignancy potential. Moreover, this differed depending on the type of mutation. Deletions and deletion-insertion type mutations were associated with worse recurrence-free survival. Duplications and substitutions, on the other hand, were associated with favorable recurrence-free survival. 

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KIT deletion/deletion-insertion, including codons 557 and 558, were especially associated with worse [recurrence-free survival],” the researchers wrote. “KIT exon 11 duplication mutations might have a favorable prognosis and warrant further investigation.”

The mutations in the KIT gene usually increase the activity of transmembrane tyrosine kinase proteins that this gene encodes. This in turn results in continuous signal transduction favoring cell growth and division over apoptosis.

The treatment for GISTs is radical and complete surgical resection. This can be followed by medical treatment with tyrosine kinase inhibitors such as imatinib mesylate to prevent recurrence and improve the survival rate.


Cho H, Nishida T, Takahashi T, Masuzawa T, Hirota S. Impact of the KIT/PDGFRA genotype on prognosis in imatinib-naïve Japanese patients with gastrointestinal stromal tumor. Ann Gastroenterol Surg. Published online November 9, 2021. doi:10.1002/ags3.12527