bims-fragic 2026-07-19 papers

Issue of 2026–07–19
two papers selected by
Laura Mannarino, Humanitas Research

Commun Biol. 2026 Jul 13.

Fragmentation-Induced Coverage Biases in Cell-Free DNA Sequencing Affect the Clinical Sensitivity of Liquid Biopsies.

Akshaya Vijayan Selvarajan, Debajyoti Kabiraj, Subhajyoti De.

Cell-free DNA (cfDNA) circulating in blood is characterized by epigenetic context-dependent fragmentation that distinguishes it from the stable genomic DNA of solid tissues. Extensive fragmentation and degradation of cfDNA can result in uneven coverage and potential loss of genetic information. Yet, its implications for the sensitivity of non-invasive detection of clinically relevant variants remain unclear. We analyzed clinical genomic data comprising 0.4 million variants across 67,129 samples from 99 cohorts spanning all major cancer types. We demonstrate that locus-specific and allele-specific coverage biases in liquid biopsy, driven by cfDNA fragmentation, affect known oncogenic hotspots in clinically actionable genes, including TP53, EGFR, and NRAS. These biases result in uneven sensitivity for detecting somatic variants. Longitudinal analysis reveals that these biases can compromise the reliability of disease tracking, potentially leading to false-negative conclusions about clonal extinction and minimal residual disease. We also urge caution while assessing clonal hematopoiesis from cfDNA sequencing.

DOI: https://doi.org/10.1038/s42003-026-10414-6

Adv Exp Med Biol. 2026 ;1501 271-301

Cell-Free DNA (cfDNA), Its Applications in Cancer Diagnosis and Monitoring, and Its Potential Role in Regulating Cancer Metabolism.

Catarina Freitas-Dias, Isabel Lemos, Stefano Mazzoleni, Jacinta Serpa.

Cell-free DNA (cfDNA) has emerged as a valuable biomarker in cancer diagnosis, monitoring, and prognosis. cfDNA refers to small fragments of DNA that are released into the bloodstream from tumor cells, normal cells, or dying cells within the body. In the context of cancer, circulating tumor DNA (ctDNA), a subset of cfDNA, contains tumor-specific genetic mutations, epigenetic alterations, and structural variations that can be used to detect the presence of cancer, track disease progression, and assess therapeutic response. Beyond its diagnostic potential, cfDNA plays a significant role in the regulation of cancer cell features and potentially cancer metabolism. Recent studies suggest that cfDNA is not merely a passive byproduct of cellular turnover but may actively influence tumor microenvironments, inflammation, and metabolic pathways, thereby impacting cancer progression. This review explores the clinical utility of cfDNA in cancer, its emerging role in metabolic regulation, and its potential to transform personalized cancer therapy by providing non-invasive, real-time insights into tumor dynamics.

Keywords: Cancer metabolic remodeling; Cell-free DNA (cfDNA); Circulating tumor DNA (ctDNA); Epigenetic control; Toll-Like receptors (TLR)

DOI: https://doi.org/10.1007/978-3-032-12166-0_10