Next Article in Journal
The B-Cell-Specific Ablation of B4GALT1 Reduces Cancer Formation and Reverses the Changes in Serum IgG Glycans during the Induction of Mouse Hepatocellular Carcinoma
Previous Article in Journal
Negative Relationship between Post-Treatment Stromal Tumor-Infiltrating Lymphocyte (TIL) and Survival in Triple-Negative Breast Cancer Patients Treated with Dose-Dense Dose-Intense NeoAdjuvant Chemotherapy
Previous Article in Special Issue
Non-Invasive Monitoring of Increased Fibrotic Tissue and Hyaluronan Deposition in the Tumor Microenvironment in the Advanced Stages of Pancreatic Ductal Adenocarcinoma
 
 
Article

Circulating Cell-Free DNA Reflects the Clonal Evolution of Breast Cancer Tumors

1
Institute of Clinical Medicine, Clinical Pathology and Forensic Medicine, University of Eastern Finland, FI-70211 Kuopio, Finland
2
Multidisciplinary Cancer Research Area, University of Eastern Finland, FI-70211 Kuopio, Finland
3
Cancer Center, Department of Oncology, Kuopio University Hospital, FI-70029 Kuopio, Finland
4
Department of Clinical Pathology, Kuopio University Hospital, FI-70029 Kuopio, Finland
5
Biobank of Eastern Finland, Kuopio University Hospital, FI-70029 Kuopio, Finland
*
Author to whom correspondence should be addressed.
Academic Editor: Nathalie A. Johnson
Cancers 2022, 14(5), 1332; https://doi.org/10.3390/cancers14051332
Received: 10 February 2022 / Revised: 28 February 2022 / Accepted: 1 March 2022 / Published: 4 March 2022
(This article belongs to the Special Issue Non-invasive Monitoring of Cancer Progression)
Liquid biopsy of cell-free DNA (cfDNA) is proposed as potential method for the early detection of breast cancer (BC) metastases and following the clonal evolution of BC. Though the use of liquid biopsy is widely discussed, only few studies have demonstrated such usage so far. The aim of this study was to evaluate how accurately cfDNA resembles the genetic profile of tumor DNA and how liquid biopsy reflects the clonal evolution of 18 Eastern-Finnish BC cases with locoregional or distant metastases. Although notable discordance between the sequenced cfDNA and tumor DNA was observed, our results show that liquid biopsy reflects the heterogeneity and clonal evolution of BC and may help to identify potential driver variants and therapeutic targets that are not detected with the sequencing of tumor DNA. This information may be used to detect metastatic BC earlier and to support decision-making in clinical practice.
Liquid biopsy of cell-free DNA (cfDNA) is proposed as a potential method for the early detection of breast cancer (BC) metastases and following the clonal evolution of BC. Though the use of liquid biopsy is a widely discussed topic in the field, only a few studies have demonstrated such usage so far. We sequenced the DNA of matched primary tumor and metastatic sites together with the matched cfDNA samples from 18 Eastern Finnish BC patients and investigated how well cfDNA reflected the clonal evolution of BC interpreted from tumor DNA. On average, liquid biopsy detected 56.2 ± 7.2% of the somatic variants that were present either in the matched primary tumor or metastatic sites. Despite the high discordance observed between matched samples, liquid biopsy was found to reflect the clonal evolution of BC and identify novel driver variants and therapeutic targets absent from the tumor DNA. Tumor-specific somatic variants were detected in cfDNA at the time of diagnosis and 8.4 ± 2.4 months prior to detection of locoregional recurrence or distant metastases. Our results demonstrate that the sequencing of cfDNA may be used for the early detection of locoregional and distant BC metastases. Observed discordance between tumor DNA sequencing and liquid biopsy supports the parallel sequencing of cfDNA and tumor DNA to yield the most comprehensive overview for the genetic landscape of BC. View Full-Text
Keywords: liquid biopsy; tumor evolution; intratumoral heterogeneity; sequencing; biomarker; recurrence; metastasis liquid biopsy; tumor evolution; intratumoral heterogeneity; sequencing; biomarker; recurrence; metastasis
Show Figures

Figure 1

MDPI and ACS Style

Kujala, J.; Hartikainen, J.M.; Tengström, M.; Sironen, R.; Auvinen, P.; Kosma, V.-M.; Mannermaa, A. Circulating Cell-Free DNA Reflects the Clonal Evolution of Breast Cancer Tumors. Cancers 2022, 14, 1332. https://doi.org/10.3390/cancers14051332

AMA Style

Kujala J, Hartikainen JM, Tengström M, Sironen R, Auvinen P, Kosma V-M, Mannermaa A. Circulating Cell-Free DNA Reflects the Clonal Evolution of Breast Cancer Tumors. Cancers. 2022; 14(5):1332. https://doi.org/10.3390/cancers14051332

Chicago/Turabian Style

Kujala, Jouni, Jaana M. Hartikainen, Maria Tengström, Reijo Sironen, Päivi Auvinen, Veli-Matti Kosma, and Arto Mannermaa. 2022. "Circulating Cell-Free DNA Reflects the Clonal Evolution of Breast Cancer Tumors" Cancers 14, no. 5: 1332. https://doi.org/10.3390/cancers14051332

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop