Genetic alterations are common in small gastrointestinal stromal tumors (GISTs), suggesting an underestimated risk of these small GISTs, a recently published study in the journal Cancers revealed.

“In this study, we aimed to investigate potential driver genes in small GISTs using whole-exome sequencing (WES) and targeted Sanger sequencing, which will contribute to an increase in the understanding of small GISTs,” the authors highlighted.

The research team initially collected 40 paired small GIST samples from the gastric muscularis propria layer obtained from the lesion sample library between January 2022 and June 2022 at the Shengjing Hospital of China Medical University.


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The obtained paired blood samples were utilized as negative controls to characterize somatic mutations using WES. The inclusion criteria were based on tumor size (<2 cm), definite pathological diagnosis, and endoscopic resection methods. After applying the inclusion criteria, a total of 36 paired small GISTs samples were analyzed by WES. Somatic mutations identified were confirmed by Sanger Sequencing.

C-KIT and PDGFRA play significant roles in the incidence and development of GISTs. Study results revealed that C-KIT mutation was predominant (76%). Exon 11 of KIT was reported to be a hotspot accounting for 65% of the overall mutations. Furthermore, mutations occurring at exons 9 and 17 constituted 6.8% and 1.4%, respectively.

Additionally, PDGFRA mutations appearing at exons 18 and 12 constituted 5% of all the mutations. In particular, 15% of the samples were found to harbor malignant BRAFV600E mutations, which had not been identified in prior studies related to GISTs. This result suggested that BRAF-mutated tumors can be described as a low-risk subtype of the small gastric GISTs.

“In this study, we demonstrated that genetic alterations are prevalent in small gastric GISTs, suggesting an underestimated risk of these small GISTs,” the authors reported. “Despite the high frequency of the BRAF-V600E mutation, these small gastric stromal tumors might be benign and represent a low-risk subtype of GISTs,” they added

More advanced sequencing methods are needed to outline the mutation status and understand the molecular basis of these small GISTs. “Molecular analysis will be helpful to facilitate personalized medicine and settle disputes related to treatment for small GISTs,” the authors concluded.

GISTs are the most prevalent mesenchymal tumors of the gastrointestinal tract. Small GISTs are defined as those with a diameter <2 cm. Generally, most small GISTs are considered low risk. However, the potential malignancy of these small GISTs cannot be ignored. Due to a lack of evidence on the explanation of epidemiology, risk factors, and etiology of these small tumors, small GIST monitoring and management have been considered controversial. Positive surgical or endoscopic resection treatment needs to be considered for small GISTs because of their universal oncogenic mutation and undefined prognosis.

Reference

Guo J, Ge Q, Yang F, et al. Small gastric stromal tumors: an underestimated risk. Cancers. Published online December 6, 2022. doi:10.3390/cancers14236008