• info@icbcongress.com
• English

ساخت اکانت کاربری رایگان

• ورود

INTERNATIONAL CONGRESS OF

CancerGenetics

• Epigenetic Footprints of Cancer in Cell-Free DNA and Their Applications in Early Cancer Detection

• Saba Adlikhatibi,^1,* SeyyedAli Bolouri,²
  1. Department of Biology university of tabriz Branch tabriz Iran
  2. Department of Biology university of tabriz Branch tabriz Iran
  
  
  
• Introduction: Cell-free DNA, or cfDNA, consists of DNA fragments that are released from cells into plasma, serum, urine, and cerebrospinal fluid. Plasma cfDNA has a short lifespan, with a half-life of approximately 15 minutes to 2.5 hours. Its analysis provides a minimally invasive approach for early cancer detection, treatment monitoring, and identification of residual disease after treatment. Genetic markers such as mutations differ among patients; therefore, epigenetic markers have attracted increasing attention because of their greater stability and generalizability.
• Methods: DNA Methylation DNA methylation is one of the most important epigenetic markers. In this process, a methyl group is added to the C5 position of cytosine, producing 5mC, and this modification occurs predominantly at CpG sites. The methylation pattern is cell-specific and regulates gene expression. In cancer, decreased methylation across the genome and increased methylation of tumor-suppressor gene promoters are observed. These changes, which may occur at early stages, have made DNA methylation an important marker for cancer detection. Methods for Detecting Methylation in cfDNA WGBS is considered the primary standard for analyzing genome-wide DNA methylation. During bisulfite conversion, unmethylated cytosines are converted to uracil, whereas methylated cytosines remain unchanged. Because cfDNA is present in small amounts and is highly fragmented, this process can result in considerable sample loss. Therefore, methods such as PBAT, scBS-seq, EM-seq, TAPS, MeDIP-seq, cfMeDIP-seq, RRBS, and cfRRBS have been developed for low-input samples.
• Results: Determination of Tissue of Origin Specific methylation patterns can identify the tissue of origin of cfDNA. MetDecode uses a reference atlas containing blood cells and tumor tissues to estimate the contribution of each tissue to cfDNA and can also model the contribution of an unknown tissue that is not included in the original atlas. Hydroxymethylation 5hmC 5hmC is generated from the conversion of 5mC by TET enzymes and is generally associated with gene activation. This marker is found in promoters, enhancers, and genes and has a tissue-specific pattern. The level of 5hmC is lower in many solid tumors than in healthy tissues. Analysis of 5hmC in cfDNA can help determine tumor type and stage. Because its level is low in blood cells, it also provides a more suitable background for identifying tissue-specific markers.
• Conclusion: DNA methylation has been identified as one of the most stable and specific footprints for determining tissue of origin. CancerLocator and CancerDetector showed sensitivities ranging from 74.4% to 94.8% at 100% specificity. In samples with a tumor fraction above 3%, MetDecode correctly identified the cancer type in 84.2% of cases. DELFI also helped determine tissue of origin through fragmentomics, and its combination with mutation analysis increased sensitivity. In clinical applications, Cologuard, Epi proColon, and Galleri are among the notable tests. However, important challenges include low sensitivity in early-stage disease, very low amounts of tumor DNA, DNA degradation during bisulfite conversion, and the lack of standardized pre-analytical and bioinformatic procedures. Developing standardized methods and combining multiple epigenetic footprints may improve the accuracy of early cancer detection. These approaches enable the analysis of cancer-related changes and provide information about tumor origin, disease status, and response to treatment.
• Keywords: Cell-free DNA; DNA methylation; Epigenetic biomarkers; Early cancer detection