Targeted Next-Generation Sequencing of Circulating Tumor DNA Mutations among Metastatic Breast Cancer Patients
Autor: | Lujia Chen, Ming Li, Xue-Xi Yang, Hong-Yan Du, Minying Sun, Hong Li, Fang-Qin Lin, Wei-Quan Lin |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty medicine.medical_treatment Breast Neoplasms medicine.disease_cause Article Deep sequencing DNA sequencing 03 medical and health sciences breast cancer 0302 clinical medicine Breast cancer targeted next-generation sequencing Internal medicine Biomarkers Tumor Humans Medicine Liquid biopsy RC254-282 circulating tumor DNA Mutation Chemotherapy business.industry High-Throughput Nucleotide Sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cancer medicine.disease Metastatic breast cancer 030104 developmental biology 030220 oncology & carcinogenesis Female mutation business |
Zdroj: | Current Oncology, Vol 28, Iss 214, Pp 2326-2336 (2021) Current Oncology Volume 28 Issue 4 Pages: 2326-2336 |
ISSN: | 1718-7729 |
Popis: | Background Liquid biopsy through the detection of circulating tumor DNA (ctDNA) has potential advantages in cancer monitoring and prediction. However, most previous studies in this area were performed with a few hotspot genes, single time point detection, or insufficient sequencing depth.Methods In this study, we performed targeted next-generation sequencing (NGS) with a customized panel in metastatic breast cancer (MBC) patients. Fifty-four plasma samples were taken before chemotherapy and after the third course of treatment for detection and analysis. Paired lymphocytes were also included to eliminate clonal hematopoiesis (CH)-related alternatives.Results A total of 1182 nonsynonymous mutations on 419 genes were identified. More ctDNA mutations were detected in patients with tumors> 3cm (P = 0.035) and HER2(−) patients (P = 0.029). For a single gene, the distribution of ctDNA mutations was also correlated with clinical characteristics. Multivariate regression analysis revealed that HER2 status was significantly associated with mutation burden (OR 0.02, 95% CI 0–0.62, P = 0.025). The profiles of ctDNA mutations exhibited marked discrepancies between two time points, and baseline ctDNA was more sensitive and specific than that after chemotherapy. Finally, elevated ctDNA mutation level was positively correlated with poor survival (P Conclusion Mutations in ctDNA could serve as a potential biomarker for the evaluation and prediction, and guide the clinical management of MBC patients with chemotherapy. |
Databáze: | OpenAIRE |
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