Cell-Free DNA Fragmentomics: A Promising Biomarker for Diagnosis, Prognosis and Prediction of Response in Breast Cancer

Gianni, Caterina; Palleschi, Michela; Merloni, Filippo; Menna, Grazia; Sirico, Marianna; Sarti, Samanta; Virga, Alessandra; Ulivi, Paola; Cecconetto, Lorenzo; Mariotti, Marita; Giorgi, Ugo De

doi:10.3390/ijms232214197

Cited by 17 publications

(16 citation statements)

References 91 publications

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“…Liquid biopsy has the potential to address the identification of possible predictive biomarkers that may guide treatment decisions, monitoring of treatment response, and identification of resistance and disease recurrence. Among BC studies, fragmentomics with ctDNA and cfDI analysis have shown their role as valuable methods to extract information from the liquid biopsy with potential applications in the clinical setting from cancer detection to evaluation of treatment response and anticipation of recurrence diagnosis [31].…”

Section: Discussionmentioning

confidence: 99%

A Case–Control Study by ddPCR of ALU 260/111 and LINE-1 266/97 Copy Number Ratio in Circulating Cell-Free DNA in Plasma Revealed LINE-1 266/97 as a Potential Biomarker for Early Breast Cancer Detection

Bortul

Giudici

Tierno

et al. 2023

IJMS

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Background: In Western countries, breast cancer (BC) is the most common cancer in women. Early detection has a positive impact on survival, quality of life, and public health costs. Mammography screening programs have increased early detection rates, but new approaches to more personalized surveillance could further improve diagnosis. Circulating cell-free DNA (cfDNA) in blood could provide a potential tool for early diagnosis by analyzing cfDNA quantity, circulating tumor DNA mutations, or cfDNA integrity (cfDI). Methods: Plasma was obtained from the blood of 106 breast cancer patients (cases) and 103 healthy women (controls). Digital droplet PCR was used for the determination of ALU 260/111 bp and LINE-1 266/97 bp copy number ratio and cfDI. cfDNA abundance was calculated using copies of the EEF1A2 gene. The accuracy of biomarker discrimination was analyzed with receiver operating characteristic curve (ROC). Sensitivity analyses were performed to account for age as a potential confounder. Results: Cases had significantly lower ALU 260/111 or LINE-1 266/97 copy number ratios (median; ALU 260/111 = 0.08, LINE-1 266/97 = 0.20), compared with control (median; ALU 260/111 = 0.10, LINE-1 266/97 = 0.28) (p < 0.001). ROC analysis showed that copy number ratio discriminated cases from controls (area under the curve, AUC = 0.69, 95% CI: 0.62–0.76 for ALU and 0.80, 95% CI: 0.73–0.86 for LINE-1). ROC from cfDI confirmed the better diagnostic performance of LINE-1 compared with ALU. Conclusions: Analysis of LINE-1 266/97 copy number ratio or cfDI by ddPCR appears to be a useful noninvasive test that could aid in early BC detection. Further studies in a large cohort are needed to validate the biomarker.

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Section: Discussionmentioning

confidence: 99%

A Case–Control Study by ddPCR of ALU 260/111 and LINE-1 266/97 Copy Number Ratio in Circulating Cell-Free DNA in Plasma Revealed LINE-1 266/97 as a Potential Biomarker for Early Breast Cancer Detection

Bortul

Giudici

Tierno

et al. 2023

IJMS

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“…Fragmentomics in liquid biopsy has emerged as a promising approach for the detection and monitoring of cancer [ 165 , 166 , 167 , 168 , 169 ]. It involves analyzing the fragmentation patterns of cfDNA using NGS technologies (such as WES or WGS) without performing the DNA sonication step or using long-read sequencing [ 129 , 170 , 171 ].…”

Section: Emerging Methods For Liquid Biopsy Biomarker Discoverymentioning

confidence: 99%

Sequence-Based Platforms for Discovering Biomarkers in Liquid Biopsy of Non-Small-Cell Lung Cancer

Brockley¹,

Souza

Forder³

et al. 2023

Cancers

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Lung cancer detection and monitoring are hampered by a lack of sensitive biomarkers, which results in diagnosis at late stages and difficulty in tracking response to treatment. Recent developments have established liquid biopsies as promising non-invasive methods for detecting biomarkers in lung cancer patients. With concurrent advances in high-throughput sequencing technologies and bioinformatics tools, new approaches for biomarker discovery have emerged. In this article, we survey established and emerging biomarker discovery methods using nucleic acid materials derived from bodily fluids in the context of lung cancer. We introduce nucleic acid biomarkers extracted from liquid biopsies and outline biological sources and methods of isolation. We discuss next-generation sequencing (NGS) platforms commonly used to identify novel biomarkers and describe how these have been applied to liquid biopsy. We highlight emerging biomarker discovery methods, including applications of long-read sequencing, fragmentomics, whole-genome amplification methods for single-cell analysis, and whole-genome methylation assays. Finally, we discuss advanced bioinformatics tools, describing methods for processing NGS data, as well as recently developed software tailored for liquid biopsy biomarker detection, which holds promise for early diagnosis of lung cancer.

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“…This term refers to applications that characterize cfDNA fragmentation and topology patterns that mirror chromatin compaction, gene regulation and the epigenome [ 132 , 135 , 136 ]. These patterns show high specificity with respect to tissue origin and disease and are thus discussed as promising cancer biomarkers [ 137 , 138 ]. While the general feasibility of this approach has been shown for HNSCC [ 133 ], fragmentomics is still in its infancy and many technical and conceptual issues need to be resolved.…”

Section: Genetic Analysis Of Circulating Cfdna In Patients With Hnsccmentioning

confidence: 99%

Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma

Brandt

Thiele

Daetwyler

et al. 2023

Cancers

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Tumors shed cell-free DNA (cfDNA) into the plasma. “Liquid biopsies” are a diagnostic test to analyze cfDNA in order to detect minimal residual cancer, profile the genomic tumor landscape, and monitor cancers non-invasively over time. This technique may be useful in patients with head and neck squamous cell carcinoma (HNSCC) due to genetic tumor heterogeneity and limitations in imaging sensitivity. However, there are technical challenges that need to be overcome for the widespread use of liquid biopsy in the clinical management of these patients. In this review, we discuss our current understanding of HNSCC genetics and the role of cfDNA genomic analyses as an emerging precision diagnostic tool.

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Cell-Free DNA Fragmentomics: A Promising Biomarker for Diagnosis, Prognosis and Prediction of Response in Breast Cancer

Cited by 17 publications

References 91 publications

A Case–Control Study by ddPCR of ALU 260/111 and LINE-1 266/97 Copy Number Ratio in Circulating Cell-Free DNA in Plasma Revealed LINE-1 266/97 as a Potential Biomarker for Early Breast Cancer Detection

A Case–Control Study by ddPCR of ALU 260/111 and LINE-1 266/97 Copy Number Ratio in Circulating Cell-Free DNA in Plasma Revealed LINE-1 266/97 as a Potential Biomarker for Early Breast Cancer Detection

Sequence-Based Platforms for Discovering Biomarkers in Liquid Biopsy of Non-Small-Cell Lung Cancer

Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma

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