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Mapping the breast cancer metastatic cascade onto ctDNA using genetic and epigenetic clonal tracking
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Mapping the breast cancer metastatic cascade onto ctDNA using genetic and epigenetic clonal tracking
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Journal Article
Mapping the breast cancer metastatic cascade onto ctDNA using genetic and epigenetic clonal tracking
2020
Overview
Circulating tumour DNA (ctDNA) allows tracking of the evolution of human cancers at high resolution, overcoming many limitations of tissue biopsies. However, exploiting ctDNA to determine how a patient’s cancer is evolving in order to aid clinical decisions remains difficult. This is because ctDNA is a mix of fragmented alleles, and the contribution of different cancer deposits to ctDNA is largely unknown. Profiling ctDNA almost invariably requires prior knowledge of what genomic alterations to track. Here, we leverage on a rapid autopsy programme to demonstrate that unbiased genomic characterisation of several metastatic sites and concomitant ctDNA profiling at whole-genome resolution reveals the extent to which ctDNA is representative of widespread disease. We also present a methylation profiling method that allows tracking evolutionary changes in ctDNA at single-molecule resolution without prior knowledge. These results have critical implications for the use of liquid biopsies to monitor cancer evolution in humans and guide treatment.
Tracking tumour evolution in a patient via circulating tumour DNA (ctDNA) is complicated due to the unknown mix of fragmented alleles from different cancer lesions. Here, the authors make use of a rapid autopsy program to demonstrate how representative ctDNA profiling is of metastasis, as well as presenting methylation profiling method to track evolutionary change.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
