Shim Hyoeun, Kwon Min Jeong, Park In Hae, Kim Min Kyeong, Cho Eun-Hae, Lee Junnam, Lee Seung-Tae, Sim Sung Hoon, Lee Keun Seok, Kim Yun-Hee, Kim Seok-Ki, Lee Eun Sook, Kong Sun-Young
Department of Laboratory Medicine, Hospital, National Cancer Center, Goyang, Korea.
Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Korea.
Ann Transl Med. 2022 Jan;10(2):28. doi: 10.21037/atm-21-4881.
Circulating tumor DNA (ctDNA) is a non-invasive biomarker for evaluating cancer prognosis. The aim of this study was to analyze the genomic profile of circulating tumor DNA (ctDNA) in breast cancer patients, and evaluate its clinical implications.
Targeted sequencing of ctDNA was performed in 38 patients using commercially available Oncomine Breast cfDNA panel. Whole exome sequencing was performed on matched tumor DNA (n=20). Survival analysis and response to chemotherapy in the study population were evaluated. The detected genomic variants were validated and serially monitored with droplet digital polymerase chain reaction (ddPCR) in 5 patients.
At least one variant or copy number alteration was detected in the ctDNA of 31 of 38 (82%) breast cancer patients, with the most common variants being in (50%), (15%) and (14%). When comparing genomic profiles of ctDNA and those of matched tumor DNA in 20 patients, the concordance rate was 9.7% among positives. The patients with variants in showed significantly poorer overall survival than those without [hazard ratio (HR) =3.90, 95% confidence interval (CI): 1.10-13.84, P=0.035] and its impact was also statistically significant in multivariate analysis with breast cancer subtype included. In serially monitored results, changes in the allele frequency of somatic variants () of ctDNA were found to be reflective of response to chemotherapy.
The genomic profile of ctDNA reflects and provides additional information to the tumor DNA genome profile. Follow-up monitoring of mutations detected in ctDNA is useful in the clinical management of breast cancer patients.
循环肿瘤DNA（ctDNA）是一种用于评估癌症预后的非侵入性生物标志物。本研究旨在分析乳腺癌患者循环肿瘤DNA（ctDNA）的基因组特征，并评估其临床意义。
使用市售的Oncomine Breast cfDNA检测板对38例患者进行ctDNA靶向测序。对匹配的肿瘤DNA（n = 20）进行全外显子测序。评估研究人群的生存分析和化疗反应。在5例患者中，用液滴数字聚合酶链反应（ddPCR）对检测到的基因组变异进行验证并连续监测。
在38例乳腺癌患者中的31例（82%）的ctDNA中检测到至少一种变异或拷贝数改变，最常见的变异发生在（50%）、（15%）和（14%）。在20例患者中比较ctDNA和匹配肿瘤DNA的基因组特征时，阳性之间的一致性率为9.7%。有变异的患者总体生存率明显低于无变异的患者[风险比（HR）= 3.90，95%置信区间（CI）：1.10 - 13.84，P = 0.035]，并且在纳入乳腺癌亚型的多变量分析中其影响也具有统计学意义。在连续监测结果中，发现ctDNA的体细胞变异（）的等位基因频率变化反映了对化疗的反应。
ctDNA的基因组特征反映并为肿瘤DNA基因组特征提供了额外信息。对ctDNA中检测到的突变进行随访监测对乳腺癌患者的临床管理有用。
