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Updated: Jun 17, 2026
Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
Published on: May 10, 2024
Mutational analysis of TTK gene in gastric and colorectal cancers with microsatellite instability
Chang Hyeok Ahn1, Yoo Ri Kim, Sung Soo Kim
1Department of General Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Purpose:
The TTK gene plays a crucial role in regulation of the mitotic checkpoint. The TTK gene has an A9 mononucleotide repeat in the coding sequences, which harbors mutations in gastric (GC) and colorectal cancers (CRC) with microsatellite instability (MSI). However, there are three more repeats (the A7s) in the coding sequences that have not been analyzed. The aim of this study was to explore whether the three A7s as well as the A9 are altered in GC and CRC, and to find any association of TTK mutation with clinocopathologic characteristics of GC and CRC.
Materials And Methods:
We analyzed exon 5 (A7 and A7) and exon 22 (A9 and A7) which have repeat sequences in 30 GC with high MSI (MSI-H), 15 GC with low MSI (MSI-L), 35 CRC with MSI-H, and 15 CRC with MSI-L, by single-strand conformation polymorphism (SSCP) and DNA sequencing assays.
Results:
Overall, we detected 23 frameshift mutations in the repeat sequences of TTK in the GC with MSI-H (11/30; 36.7%) and the CRC with MSI-H (12/35; 34.3%), but not in the cancers with MSI-L. The mutations were observed in both A9 and A7 of exon 22, but in neither of the two A7s of exon 5. The mutations consisted of c.2560delA, c.2560dupA, c.2571delA and c.[2560delA(+)2571delA]. All of the mutations were frameshift mutations and would result in premature stops of TTK protein synthesis. There was no significant difference in clinopathologic parameters of the cancers with the mutations.
Conclusion:
Our data indicate that frameshift mutations of TTK are common in both GC and CRC with MSI-H, and that the mutations occur not only in the A9 repeat but also in the A7 repeat. The data suggest that frameshift mutations of TTK might alter cell cycle control in the affected cells and contribute to pathogenesis of cancers with MSI-H.
Insights
Frameshift mutations in the TTK gene are common in gastric (GC) and colorectal cancers (CRC) with microsatellite instability (MSI-H). These TTK gene mutations affect both A9 and A7 repeats, potentially impacting cell cycle control in cancer development.
Area of Science:
- Genetics and Genomics
- Cancer Biology
- Molecular Oncology
Background:
- The TTK gene is vital for mitotic checkpoint regulation.
- Previous studies identified TTK gene A9 repeat mutations in gastric (GC) and colorectal cancers (CRC) with microsatellite instability (MSI).
- The role of other TTK repeats (A7s) in GC and CRC remained uninvestigated.
Purpose of the Study:
- To investigate alterations in TTK gene A7 and A9 repeats in GC and CRC.
- To determine the association between TTK mutations and clinocopathologic features of GC and CRC.
Main Methods:
- Analysis of TTK gene exon 5 (A7, A7) and exon 22 (A9, A7) in GC and CRC samples.
- Samples included high microsatellite instability (MSI-H) and low microsatellite instability (MSI-L) subtypes.
- Techniques used were single-strand conformation polymorphism (SSCP) and DNA sequencing.
Main Results:
- Frameshift mutations in TTK repeats were detected in 36.7% of GC-MSI-H and 34.3% of CRC-MSI-H.
- Mutations occurred in both A9 and A7 repeats of exon 22, but not in exon 5 repeats.
- No significant association was found between TTK mutations and clinocopathologic parameters.
Conclusions:
- Frameshift mutations in TTK gene repeats are frequent in GC and CRC with MSI-H.
- These mutations affect both A9 and A7 repeats, leading to premature TTK protein termination.
- TTK mutations may contribute to the pathogenesis of MSI-H cancers by disrupting cell cycle control.
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