bims-dinmec Biomed News
on DNA methylation in cancer
Issue of 2025–09–14
two papers selected by
Lorena Ancona, Humanitas Research



  1. Cell Rep Methods. 2025 Jul 21. pii: S2667-2375(25)00119-5. [Epub ahead of print]5(7): 101083
      We introduce a cell-free DNA (cfDNA) fragmentation pattern: the fragment dispersity index (FDI), which integrates information on the distribution of cfDNA fragment ends with the variation in fragment coverage, enabling precise characterization of chromatin accessibility in specific regions. The FDI shows a strong correlation with chromatin accessibility and gene expression, and regions with high FDI are enriched in active regulatory elements. Using whole-genome cfDNA data from five datasets, we developed and validated the FDI-oncology model, which demonstrates robust performance in early cancer diagnosis, subtyping, and prognosis. Case studies reveal that key cancer genes such as HER2 and TP53 exhibit significantly different FDIs between cancer and control samples. Simulation experiments suggest that deep targeted sequencing of a small number of regions can achieve high diagnostic efficiency.
    Keywords:  CP: cancer biology; CP: systems biology; cancer early detection; cfDNA; liquid biopsy; machine learning
    DOI:  https://doi.org/10.1016/j.crmeth.2025.101083
  2. Nat Rev Cancer. 2025 Sep 08.
      Somatic mutations in several genes, including key oncogenes and tumour suppressor genes, are present from early life and can accumulate as an individual ages, indicating that the potential for cancer is present and growing throughout life. However, the risk of developing cancer rises sharply after 50-60 years of age, suggesting that the ability of these mutations to undergo clonal expansion and drive cancer development is dependent on the progressive changes in the epigenome and microenvironment that occur during ageing. Epigenetic changes, including DNA methylation and histone modifications, can drive various hallmarks of ageing in precancerous cells, including induction of senescence, the senescence-associated secretory phenotype, genomic instability and reduction of nuclear integrity, metabolic and inflammatory stress responses, stem cell function and differentiation potential, and redox balance. This can also alter the normal immune and stromal cells in the tissue microenvironment, which cumulatively enhances the effects of cancer driver mutations, ultimately promoting cancer development and progression in aged individuals. Unravelling these mechanisms will provide novel preventive and therapeutic strategies to limit the burden and progression of cancer in aged individuals.
    DOI:  https://doi.org/10.1038/s41568-025-00868-x