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Updated: Sep 21, 2025
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Comparative analysis of cancer gene mutations using targeted sequencing in matched primary and recurrent gastric
Yeon-Ju Huh1,2, Sung-Yup Cho3,4,5, Min-Sun Cho6
1Department of Surgery, Ewha Womans University School of Medicine, Anyangcheon-ro, Yangcheon-gu, 1071, Seoul, Korea.
Background:
Investigation of responsiveness-associated genes using longitudinal mutation analyses after standard treatments in recurrent gastric cancer (GC) is limited.
Objective:
To evaluate the somatic mutations associated with resistance to combined treatment involving fluorouracil (FU) or platinum (PL) in advanced GC.
Methods:
Samples from patients with advanced GC treated with FU or PL alone, or surgery plus FU/PL, were studied. GC patients who relapsed after standard chemotherapy (FU/PL) and with presence of tumor samples from initial diagnosis and recurrence were included. Targeted sequencing analysis of 143 cancer-related genes was performed using an Oncomine Comprehensive Cancer Panel.
Results:
Matched samples of primary and recurrent lesions were analyzed in sixteen patients with GC. When genes with recurrent mutations in two or more patients were used as specific findings, a total of 26 genes were found. TP53 was the most predominantly increased allele frequency (AF) in recurrent GCs after standard treatment. The mutational AF of ERBB2, PTEN, and BRCA2 also commonly increased, suggesting the role of these mutations in treatment resistance, whereas the mutational AF of VLH, NF1, and STK11 frequently decreased in recurrent tumors, suggesting the role of these mutations in increasing sensitivity to treatment. TCGA gastric cancer data (n = 436) were analyzed, and mutation sites detected in 16 GC patients in this study were in agreement with TCGA cohort with some exceptions. Overall survival according to gene expression associated with chemotherapy responsiveness exhibited compatible patterns with gain or loss-of-function mutations of each gene.
Conclusions:
Mutations in TP53, ERBB2, PTEN, BRCA2, VHL, NF1, and STK11 are candidate somatic alterations related to chemoresistance in GC.
Insights
Somatic mutations in TP53, ERBB2, PTEN, and BRCA2 may drive chemoresistance in gastric cancer (GC). Conversely, decreased mutations in VHL, NF1, and STK11 suggest increased sensitivity to treatment.
Area of Science:
- Oncology
- Genetics
- Cancer Research
Background:
- Longitudinal mutation analyses in recurrent gastric cancer (GC) are limited.
- Understanding genes associated with treatment response is crucial for advancing GC therapy.
Purpose of the Study:
- To identify somatic mutations linked to resistance against fluorouracil (FU) or platinum (PL) chemotherapy in advanced GC.
- To investigate the role of specific gene mutations in acquired chemoresistance.
Main Methods:
- Targeted sequencing of 143 cancer-related genes was performed on tumor samples from GC patients with initial and relapsed disease.
- Analysis included matched primary and recurrent tumor samples from 16 GC patients.
- TCGA gastric cancer data (n=436) were used for cohort comparison.
Main Results:
- TP53 showed the highest increase in allele frequency (AF) in recurrent GC post-treatment.
- Increased AF of ERBB2, PTEN, and BRCA2 suggested a role in treatment resistance.
- Decreased AF of VHL, NF1, and STK11 indicated potential increased sensitivity to treatment.
Conclusions:
- TP53, ERBB2, PTEN, and BRCA2 mutations are candidate somatic alterations associated with chemoresistance in GC.
- VHL, NF1, and STK11 mutations may be linked to increased chemosensitivity.
- Findings provide insights into genetic mechanisms of chemotherapy response and resistance in GC.
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