Abstract
Objectives
Clonal hematopoiesis (CH) is a condition in which healthy individuals have somatic mutations in hematopoietic stem cells. It has been reported with increased risk of hematologic malignancy and cardiovascular disease in the general population, but studies of Korean populations with comorbid disease entities are scarce.
Methods
White blood cells (WBCs) from patients with gastric cancer (GC) (n=121) were analyzed using a DNA-based targeted (531 genes) panel with customized pipeline designed to detect single nucleotide variants and small indels with low-allele-frequency of ≥0.2 %. We defined significant CH variants as having variant allele frequency (VAF) ≥2 % among variants found in WBCs. Matched cell-free DNA (cfDNA) samples were also analyzed with the same pipeline to investigate the false-positive results caused by WBC variants in cfDNA profiling.
Results
Significant CH variants were detected in 29.8 % of patients and were associated with age and male sex. The number of CH variants was associated with a history of anti-cancer therapy and age. DNMT3A and TET2 were recurrently mutated. Overall survival rate of treatment-naïve patients with stage IV GC was higher in those with CH, but Cox regression showed no significant association after adjustment for age, sex, anti-cancer therapy, and smoking history. In addition, we analyzed the potential interference of WBC variants in plasma cell-free DNA testing, which has attracted interest as a complementary method for tissue biopsy. Results showed that 37.0 % (47/127) of plasma specimens harbored at least one WBC variant. VAFs of interfering WBC variants in the plasma and WBC were correlated, and WBC variants with VAF ≥4 % in WBC were frequently detected in plasma with the same VAF.
Conclusions
This study revealed the clinical impact of CH in Korean patients and suggests the potential for its interference in cfDNA tests.
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Research funding: This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (to SYR, HA15C0005), a grant from the National Research Foundation of Korea (to SS, 2021R1I1A1A01045980) and supported by the MD-PhD/Medical Scientist Training Program through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (to KSL, no applicable grant number).
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. KSL, C-KL, SYR, S-TL, and JRC performed research, KSL performed data analysis, WSK and SP managed specimen collection, KSL and SS wrote the manuscript, SSK, SYR reviewed the manuscript, SYR and SS supervised the study.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: This study was approved by the Institutional Review Board of Yonsei University, Severance Hospital (IRB No. 4-2022-0422). All research procedures conformed to the principles of the Helsinki Declaration.
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Data availability: The datasets used and/or analyzed during the current study are available from the corresponding author (SS) on reasonable request.
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Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/cclm-2023-0261).
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