Targeted Next-Generation Sequencing of Circulating Tumor DNA Mutations among Metastatic Breast Cancer Patients
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. In this study, we per...
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/28/4/214 |
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| author | Min-Ying Sun Fang-Qin Lin Lu-Jia Chen Hong Li Wei-Quan Lin Hong-Yan Du Xue-Xi Yang Ming Li |
| author_facet | Min-Ying Sun Fang-Qin Lin Lu-Jia Chen Hong Li Wei-Quan Lin Hong-Yan Du Xue-Xi Yang Ming Li |
| author_sort | Min-Ying Sun |
| collection | DOAJ |
| description | 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. 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. A total of 1182 nonsynonymous mutations in 419 genes were identified. More ctDNA mutations were detected in patients with tumors > 3 cm (<i>p</i> = 0.035) and HER2(−) patients (<i>p</i> = 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 (<i>OR</i> 0.02, 95% <i>CI</i> 0–0.62, <i>p</i> = 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 (<i>p</i> < 0.001). Mutations in ctDNA could serve as a potential biomarker for the evaluation, prediction, and clinical management guidance of MBC patients with chemotherapy. |
| first_indexed | 2024-03-10T08:01:01Z |
| format | Article |
| id | doaj.art-6ab5da4764384f74b126c77b27a9707d |
| institution | Directory Open Access Journal |
| issn | 1198-0052 1718-7729 |
| language | English |
| last_indexed | 2024-03-10T08:01:01Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Oncology |
| spelling | doaj.art-6ab5da4764384f74b126c77b27a9707d2023-11-22T11:26:15ZengMDPI AGCurrent Oncology1198-00521718-77292021-06-012842326233610.3390/curroncol28040214Targeted Next-Generation Sequencing of Circulating Tumor DNA Mutations among Metastatic Breast Cancer PatientsMin-Ying Sun0Fang-Qin Lin1Lu-Jia Chen2Hong Li3Wei-Quan Lin4Hong-Yan Du5Xue-Xi Yang6Ming Li7Institute of Antibody Engineering, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, ChinaGZMU-GIBH School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, ChinaNanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaNanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaDepartment of Primary Public Health, Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, ChinaInstitute of Antibody Engineering, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, ChinaInstitute of Antibody Engineering, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, ChinaInstitute of Antibody Engineering, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, ChinaLiquid 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. 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. A total of 1182 nonsynonymous mutations in 419 genes were identified. More ctDNA mutations were detected in patients with tumors > 3 cm (<i>p</i> = 0.035) and HER2(−) patients (<i>p</i> = 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 (<i>OR</i> 0.02, 95% <i>CI</i> 0–0.62, <i>p</i> = 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 (<i>p</i> < 0.001). Mutations in ctDNA could serve as a potential biomarker for the evaluation, prediction, and clinical management guidance of MBC patients with chemotherapy.https://www.mdpi.com/1718-7729/28/4/214circulating tumor DNAmutationbreast cancertargeted next-generation sequencing |
| spellingShingle | Min-Ying Sun Fang-Qin Lin Lu-Jia Chen Hong Li Wei-Quan Lin Hong-Yan Du Xue-Xi Yang Ming Li Targeted Next-Generation Sequencing of Circulating Tumor DNA Mutations among Metastatic Breast Cancer Patients Current Oncology circulating tumor DNA mutation breast cancer targeted next-generation sequencing |
| title | Targeted Next-Generation Sequencing of Circulating Tumor DNA Mutations among Metastatic Breast Cancer Patients |
| title_full | Targeted Next-Generation Sequencing of Circulating Tumor DNA Mutations among Metastatic Breast Cancer Patients |
| title_fullStr | Targeted Next-Generation Sequencing of Circulating Tumor DNA Mutations among Metastatic Breast Cancer Patients |
| title_full_unstemmed | Targeted Next-Generation Sequencing of Circulating Tumor DNA Mutations among Metastatic Breast Cancer Patients |
| title_short | Targeted Next-Generation Sequencing of Circulating Tumor DNA Mutations among Metastatic Breast Cancer Patients |
| title_sort | targeted next generation sequencing of circulating tumor dna mutations among metastatic breast cancer patients |
| topic | circulating tumor DNA mutation breast cancer targeted next-generation sequencing |
| url | https://www.mdpi.com/1718-7729/28/4/214 |
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