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Tissue-specific cell-free DNA degradation quantifies circulating tumor DNA burden
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Journal Article
Tissue-specific cell-free DNA degradation quantifies circulating tumor DNA burden
2021
Overview
Profiling of circulating tumor DNA (ctDNA) may offer a non-invasive approach to monitor disease progression. Here, we develop a quantitative method, exploiting local tissue-specific cell-free DNA (cfDNA) degradation patterns, that accurately estimates ctDNA burden independent of genomic aberrations. Nucleosome-dependent cfDNA degradation at promoters and first exon-intron junctions is strongly associated with differential transcriptional activity in tumors and blood. A quantitative model, based on just 6 regulatory regions, could accurately predict ctDNA levels in colorectal cancer patients. Strikingly, a model restricted to blood-specific regulatory regions could predict ctDNA levels across both colorectal and breast cancer patients. Using compact targeted sequencing (<25 kb) of predictive regions, we demonstrate how the approach could enable quantitative low-cost tracking of ctDNA dynamics and disease progression.
Circulating tumour DNA (ctDNA) represents a non-invasive option to monitor cancer progression. Here, the authors perform deep sequencing of plasma cell-free DNA, and find that nucleosome-dependent cfDNA degradation at 6 specific regulatory regions is predictive of ctDNA burden.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45/23
/ 631/1647
/ Blood
/ Cancer
/ Cell-Free Nucleic Acids - blood
/ Cell-Free Nucleic Acids - genetics
/ Cell-Free Nucleic Acids - metabolism
/ Circulating Tumor DNA - genetics
/ Circulating Tumor DNA - metabolism
/ Colonic Neoplasms - genetics
/ Colorectal Neoplasms - genetics
/ DNA
/ Gene Expression Regulation, Neoplastic
/ Genomics
/ Humanities and Social Sciences
/ Humans
/ Mutation
/ Science
/ Tumors
