Accepted Preprint (first posted online 13 January 2016)

    Methylated circulating tumor DNA in blood: power in cancer prognosis and response

    1. Goli Samimi
    1. K Warton, Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, Australia
    2. K Mahon, Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, Australia
    3. G Samimi, Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, Australia
    1. Correspondence: Goli Samimi, Email: g.samimi{at}garvan.org.au

    Abstract

    Circulating tumor DNA (ctDNA) in the plasma or serum of cancer patients provides an opportunity for non-invasive sampling of tumor DNA. This 'liquid biopsy' allows for interrogations of DNA such as quantity, chromosomal alterations, sequence mutations and epigenetic changes, and can be used to guide and improve treatment throughout the course of the disease. This tremendous potential for real-time "tracking" in a cancer patient has led to substantial research efforts in the ctDNA field. ctDNA can be distinguished from non-tumor DNA by the presence of tumor-specific mutations and copy number variations, and also by aberrant DNA methylation, with both DNA sequence and methylation changes corresponding to those found in the tumor. Aberrant methylation of specific promoter regions can be a very consistent feature of cancer, in contrast to mutations, which typically occur at a wide range of sites. This consistency makes ctDNA methylation amenable to the design of widely applicable clinical assays. In this review, we examine ctDNA methylation in the context of monitoring disease status, treatment response, and determining prognosis of cancer patients.

    • Received 21 July 2015
    • Revision received 6 January 2016
    • Accepted 13 January 2016
    • Accepted Preprint first posted online on 13 January 2016