Molecular landscape and clinical significance of exon 11 mutations in KIT gene among patients with gastrointestinal stromal tumor: a retrospective exploratory study

Ruihua Zhao; Tianqi An; Min Liu; Yanan Zhou; Rui Li; Guozhong Jiang; Jing Li; Xinguang Cao; Hong Zong

doi:10.3389/fonc.2023.1272046

Molecular landscape and clinical significance of exon 11 mutations in KIT gene among patients with gastrointestinal stromal tumor: a retrospective exploratory study

Front Oncol. 2023 Oct 12:13:1272046. doi: 10.3389/fonc.2023.1272046. eCollection 2023.

Authors

Ruihua Zhao¹, Tianqi An¹, Min Liu², Yanan Zhou³, Rui Li⁴, Guozhong Jiang⁵, Jing Li², Xinguang Cao⁶, Hong Zong¹

Affiliations

¹ Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Department of Medical Science, Berry Oncology Corporation, Beijing, China.
³ Department of Endoscopy Center, Anyang Cancer Hospital, Anyang, China.
⁴ Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
⁵ Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁶ Department of Digestive Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract

Objective: This aim of this study was to investigate the prognostic significance of KIT exon 11 mutation subtypes in patients with GISTs.

Methods: A total of 233 consecutive patients diagnosed with GISTs at the First Affiliated Hospital of Zhengzhou University from January 2013 to August 2018 were included in this study. The prevalence and mutation landscape of exon 11 in KIT was presented. The clinicopathological characteristics and prognosis among the different mutation subtypes were analyzed. All the statistical analyses were performed by SPSS22.0.

Results: Somatic mutational analysis indicated that point mutations were the most frequently detected mutations followed by deletions & compound mutations and insertion and tandem duplication mutations in the stomach. Point mutations showed a low mitotic count and a high risk of recurrence, and deletions and compound mutations have a high mitotic count while insertions and tandem duplication mutations showed a low mitotic count with an intermediate recurrence risk. Point mutations and deletions frequently occurred in sequence region codons 550-560 of exon 11, while compound mutations, insertion, and tandem duplication were mainly detected in codons 557-559, 572-580, and 577-581, respectively. The multi-variation analysis demonstrated that tumor diameter and high recurrence risk groups had worse prognostic values. However, mutation types were not significant predictors of relapse-free survival (RFS) in GISTs. Survival analysis suggested no significant difference in RFS between the 557/558 deletion and the other deletions.

Conclusion: This study suggested that mutations in exon 11 of the KIT gene were common with intermediate/high recurrence risk in GISTs patients. Tumor diameter ≥5 cm, and deletions mutations might predict a worse prognosis.

Keywords: KIT exon 11; gastrointestinal stromal tumors; mutation; prognosis; sanger sequencing.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the Henan Natural Science Foundation (202300410383). The funders had no role in data analysis, the decision to publish or preparation of the manuscript.