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Early detection of colorectal cancer somatic mutations using cfDNA liquid biopsies in a murine carcinogenesis model. | LitMetric

AI Article Synopsis

  • * The study utilized a mouse model to identify oncogenic mutations associated with CRC, using advanced techniques to enhance the sensitivity of cfDNA detection during early tumor development.
  • * Results indicate that cfDNA concentration increases with cancer progression, and its non-invasive testing outperforms traditional imaging methods, highlighting its potential for early CRC detection in humans.

Article Abstract

Colorectal cancer (CRC) is one of the top five cancers in incidence and mortality worldwide. The early detection of this neoplasm through analysis of circulating free DNA (cfDNA), which carries tumor genetic alterations, as a liquid biopsy, could have a major impact in enhancing early detection and reducing the mortality rate. The aim of this work was to demonstrate the feasibility of using cfDNA as a liquid biopsy for the early detection of CRC. For this purpose, we implemented an azoxymethane and dextran sodium sulfate-induced murine carcinogenesis model to detect oncogenic somatic mutations in and during CRC development. To enhance the sensitivity in the detection, E-ice-COLD-PCR was utilized to selectively enrich for mutant alleles, followed by massively parallel sequencing. Driving somatic mutations were detected in and in the liquid biopsies of early stages of tumor development, corresponding to the formation of aberrant crypt foci, the first histological alterations that can be identified throughout the formation of CRC. The concentration of cfDNA was increased along the carcinogenic process. Polyclonality in was found in tumor samples and cfDNA in this model. On the other hand, the use of cfDNA as a non-invasive test resulted in superior early detection compared to microPET/CT imaging. As a proof-of-principle, this study shows the great potential use of allelic-specific PCR for the detection and enrichment of pathogenic alleles present in cfDNA samples, as a test for early non-invasive detection of CRC. This work provides scientific evidence to set methodological bases that allow early detection of mutations in cfDNA obtained from plasma of CRC in humans.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9608204PMC
http://dx.doi.org/10.7150/jca.76516DOI Listing

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