Smilkou Stavroula, Ntzifa Aliki, Tserpeli Victoria, Balgkouranidou Ioanna, Papatheodoridi Alkistis, Razis Evangelia, Linardou Helena, Papadimitriou Christos, Psyrri Amanda, Zagouri Flora, Kakolyris Stylianos, Lianidou Evi
Analysis of Circulating Tumor Cells Lab, Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Greece.
Department of Medical Oncology, University General Hospital of Alexandroupolis, Greece.
Mol Oncol. 2025 Jan 4. doi: 10.1002/1878-0261.13787.
Plasma cell-free DNA (cfDNA) analysis to track estrogen receptor 1 (ESR1) mutations is highly beneficial for the identification of tumor molecular dynamics and the improvement of personalized treatments for patients with metastatic breast cancer (MBC). Plasma-cfDNA is, up to now, the most frequent liquid biopsy analyte used to evaluate ESR1 mutational status. Circulating tumor cell (CTC) enumeration and molecular characterization analysis provides important clinical information in patients with MBC. In this study, we investigated whether analysis of CTCs and circulating tumor DNA (ctDNA) provide similar or complementary information for the analysis of ESR1 mutations. We analyzed both plasma-cfDNA (n = 90) and paired CTC-derived genomic DNA (gDNA; n = 42) from 90 MBC patients for seven ESR1 mutations. Eight out of 90 (8.9%) plasma-cfDNA samples tested using the ddPLEX Mutation Detection Assay (Bio-Rad, Hercules, CA, USA), were found positive for one ESR1 mutation, whereas 11/42 (26.2%) CTC-derived gDNA samples were found positive for at least one ESR1 mutation. Direct comparison of paired samples (n = 42) revealed that the ESR1 mutation rate was higher in CTC-derived gDNA (11/42, 26.2%) than in plasma-cfDNA (6/42, 14.3%) samples. Our results, using this highly sensitive ddPLEX assay, reveal a higher percentage of mutations in CTC-derived gDNAs than in paired ctDNA in patients with MBC. CTC-derived gDNA analysis should be further evaluated as an important and complementary tool to ctDNA for identifying patients with ESR1 mutations and for guiding individualized therapy.
血浆游离DNA（cfDNA）分析用于追踪雌激素受体1（ESR1）突变，对识别肿瘤分子动态以及改善转移性乳腺癌（MBC）患者的个性化治疗非常有益。截至目前，血浆cfDNA是用于评估ESR1突变状态最常用的液体活检分析物。循环肿瘤细胞（CTC）计数和分子特征分析为MBC患者提供了重要的临床信息。在本研究中，我们调查了CTC和循环肿瘤DNA（ctDNA）分析对于ESR1突变分析是否能提供相似或互补的信息。我们分析了90例MBC患者的血浆cfDNA（n = 90）和配对的CTC来源基因组DNA（gDNA；n = 42）中的7种ESR1突变。使用ddPLEX突变检测分析（美国加利福尼亚州赫拉克勒斯市伯乐公司）检测的90份血浆cfDNA样本中，有8份（8.9%）检测到一种ESR1突变呈阳性，而42份CTC来源的gDNA样本中有11份（26.2%）检测到至少一种ESR1突变呈阳性。配对样本（n = 42）的直接比较显示，CTC来源的gDNA中ESR1突变率（11/42，26.2%）高于血浆cfDNA（6/42，14.3%）样本。我们使用这种高灵敏度ddPLEX分析的结果显示，MBC患者中CTC来源的gDNA突变百分比高于配对的ctDNA。对于识别ESR1突变患者和指导个体化治疗，CTC来源的gDNA分析应作为ctDNA重要的补充工具进行进一步评估。
