Abstract
The fine-scale cell-free DNA fragmentation patterns in early-stage cancers are poorly understood. We developed a de novo approach to characterize the cell-free DNA fragmentation hotspots from plasma whole-genome sequencing. Hotspots are enriched in open chromatin regions, and, interestingly, 3′end of transposons. Hotspots showed global hypo-fragmentation in early-stage liver cancers and are associated with genes involved in the initiation of hepatocellular carcinoma and associated with cancer stem cells. The hotspots varied across multiple early-stage cancers and demonstrated high performance for the diagnosis and identification of tissue-of-origin in early-stage cancers. We further validated the performance with a small number of independent case–control-matched early-stage cancer samples.
| Original language | English (US) |
|---|---|
| Article number | 138 |
| Journal | Genome Medicine |
| Volume | 14 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 2022 |
Funding
The authors greatly acknowledge Dr. Yuk Ming Dennis Lo and his circulating nucleic acids research group in the Chinese University of Hong Kong, Dr. Jay Shendure and his research group in the University of Washington, and Drs. Robert B. Scharpf and Victor E. Velculescu and their research group in the Johns Hopkins University School of Medicine for their cfDNA data. The authors acknowledge Dr. Li Wang for her suggestions and comments on the manuscript. The authors also acknowledge Jeanette M. Buckholz for the significant effort she invested in locating the study subjects. This work is supported by the computational resources from Biomedical Informatics (BMI) high-performance computing cluster in CCHMC. The authors greatly acknowledge Dr. Yuk Ming Dennis Lo and his circulating nucleic acids research group in the Chinese University of Hong Kong, Dr. Jay Shendure and his research group in the University of Washington, and Drs. Robert B. Scharpf and Victor E. Velculescu and their research group in the Johns Hopkins University School of Medicine for their cfDNA data. The authors acknowledge Dr. Li Wang for her suggestions and comments on the manuscript. The authors also acknowledge Jeanette M. Buckholz for the significant effort she invested in locating the study subjects. This work is supported by the computational resources from Biomedical Informatics (BMI) high-performance computing cluster in CCHMC.
Keywords
- Cancer early detection
- Cell-free DNA
- Fragmentation hotspots
- Open chromatin regions
- Tissues-of-origin
ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
- Molecular Medicine
- Molecular Biology
