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Title: Tissue-specific cell-free DNA degradation quantifies circulating tumor DNA burden
Authors: Zhu, Guanhua
Guo, Yu A.
Ho, Danliang
Poon, Polly
Poh, Zhong Wee
Wong, Pui Mun
Gan, Anna
Chang, Mei Mei
Kleftogiannis, Dimitrios
Lau, Yi Ting
Tay, Brenda
Lim, Wan Jun
Chua, Clarinda
Tan, Tira J. 
Koo, Si-Lin
Chong, Dawn Q.
Yap, Yoon Sim
Tan, Iain 
Ng, Sarah
Skanderup, Anders J.
Issue Date: 13-Apr-2021
Publisher: Nature Research
Citation: Zhu, Guanhua, Guo, Yu A., Ho, Danliang, Poon, Polly, Poh, Zhong Wee, Wong, Pui Mun, Gan, Anna, Chang, Mei Mei, Kleftogiannis, Dimitrios, Lau, Yi Ting, Tay, Brenda, Lim, Wan Jun, Chua, Clarinda, Tan, Tira J., Koo, Si-Lin, Chong, Dawn Q., Yap, Yoon Sim, Tan, Iain, Ng, Sarah, Skanderup, Anders J. (2021-04-13). Tissue-specific cell-free DNA degradation quantifies circulating tumor DNA burden. Nature Communications 12 (1) : 2229. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: 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. © 2021, The Author(s).
Source Title: Nature Communications
ISSN: 2041-1723
DOI: 10.1038/s41467-021-22463-y
Rights: Attribution 4.0 International
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