Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Clin Chem Lab Med. 2023 Jul 13;62(1):178-186. doi: 10.1515/cclm-2023-0261. Print 2024 Jan 26.
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.
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.
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. and 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.
This study revealed the clinical impact of CH in Korean patients and suggests the potential for its interference in cfDNA tests.
克隆性造血（CH）是一种个体的造血干细胞存在体细胞突变的情况。在普通人群中，它与血液恶性肿瘤和心血管疾病的风险增加有关，但针对合并有合并症的韩国人群的研究却很少。
使用基于 DNA 的靶向（531 个基因）面板分析胃癌（GC）患者的白细胞（WBC），该面板采用了专门设计的定制化流程，用于检测具有低等位基因频率（≥0.2%）的单核苷酸变异和小的插入缺失。我们将具有 WBC 中发现的变异等位基因频率（VAF）≥2%的显著 CH 变异定义为阳性。还使用相同的流程分析了匹配的无细胞游离 DNA（cfDNA）样本，以研究 WBC 变异在 cfDNA 谱分析中引起的假阳性结果。
在 29.8%的患者中检测到显著的 CH 变异，且与年龄和男性有关。CH 变异的数量与抗癌治疗史和年龄有关。 和 是高频突变基因。无 CH 的 IV 期 GC 患者的治疗初治总生存率更高，但 Cox 回归显示在调整年龄、性别、抗癌治疗和吸烟史后无显著相关性。此外，我们分析了 WBC 变异对血浆无细胞游离 DNA 检测的潜在干扰，这种方法作为组织活检的补充方法引起了关注。结果表明，至少有一个 WBC 变异的血浆标本占 37.0%（47/127）。血浆和 WBC 中干扰性 WBC 变异的 VAF 相关，并且在 WBC 中 VAF≥4%的 WBC 变异在血浆中也常以相同的 VAF 检出。
本研究揭示了 CH 对韩国患者的临床影响，并提示其对 cfDNA 检测的潜在干扰。
