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Tissue-specific cell-free DNA degradation quantifies circulating tumor DNA burden

Author

Listed:
  • Guanhua Zhu

    (Genome Institute of Singapore (GIS), A*STAR)

  • Yu A. Guo

    (Genome Institute of Singapore (GIS), A*STAR)

  • Danliang Ho

    (Genome Institute of Singapore (GIS), A*STAR)

  • Polly Poon

    (Genome Institute of Singapore (GIS), A*STAR)

  • Zhong Wee Poh

    (Genome Institute of Singapore (GIS), A*STAR)

  • Pui Mun Wong

    (Genome Institute of Singapore (GIS), A*STAR)

  • Anna Gan

    (Genome Institute of Singapore (GIS), A*STAR)

  • Mei Mei Chang

    (Genome Institute of Singapore (GIS), A*STAR)

  • Dimitrios Kleftogiannis

    (Genome Institute of Singapore (GIS), A*STAR)

  • Yi Ting Lau

    (Genome Institute of Singapore (GIS), A*STAR)

  • Brenda Tay

    (National Cancer Center Singapore)

  • Wan Jun Lim

    (National Cancer Center Singapore)

  • Clarinda Chua

    (National Cancer Center Singapore)

  • Tira J. Tan

    (National Cancer Center Singapore)

  • Si-Lin Koo

    (National Cancer Center Singapore)

  • Dawn Q. Chong

    (National Cancer Center Singapore)

  • Yoon Sim Yap

    (National Cancer Center Singapore)

  • Iain Tan

    (Genome Institute of Singapore (GIS), A*STAR
    National Cancer Center Singapore
    National University of Singapore)

  • Sarah Ng

    (Genome Institute of Singapore (GIS), A*STAR)

  • Anders J. Skanderup

    (Genome Institute of Singapore (GIS), A*STAR
    National Cancer Center Singapore)

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 (

Suggested Citation

  • Guanhua Zhu & Yu A. Guo & Danliang Ho & Polly Poon & Zhong Wee Poh & Pui Mun Wong & Anna Gan & Mei Mei Chang & Dimitrios Kleftogiannis & Yi Ting Lau & Brenda Tay & Wan Jun Lim & Clarinda Chua & Tira J, 2021. "Tissue-specific cell-free DNA degradation quantifies circulating tumor DNA burden," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22463-y
    DOI: 10.1038/s41467-021-22463-y
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    Cited by:

    1. Anna-Lisa Doebley & Minjeong Ko & Hanna Liao & A. Eden Cruikshank & Katheryn Santos & Caroline Kikawa & Joseph B. Hiatt & Robert D. Patton & Navonil De Sarkar & Katharine A. Collier & Anna C. H. Hoge , 2022. "A framework for clinical cancer subtyping from nucleosome profiling of cell-free DNA," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Mingyun Bae & Gyuhee Kim & Tae-Rim Lee & Jin Mo Ahn & Hyunwook Park & Sook Ryun Park & Ki Byung Song & Eunsung Jun & Dongryul Oh & Jeong-Won Lee & Young Sik Park & Ki-Won Song & Jeong-Sik Byeon & Bo H, 2023. "Integrative modeling of tumor genomes and epigenomes for enhanced cancer diagnosis by cell-free DNA," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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