Characterization of Cell Free Plasma Methyl-DNA From Xenografted Tumors to Guide the Selection of Diagnostic Markers for Early-Stage Cancers
Circulating cell-free methyl-DNA (mcfDNA) contains promising cancer markers but its low abundance and possibly diverse origin pose challenges toward the accurate diagnosis of early stage cancers. By whole-genome bisulfite sequencing (WGBS) of cell-free DNA (cfDNA) from about 0.5 mL plasma of mice xenografted with human tumors, we obtained and aligned the reads to the human genome, filtered out the mouse and carrier bacterial sequences, and confirmed the tumor origin of methyl-cfDNA (mctDNA) by methylation-sensitive restriction enzyme digestion prior to species-specific PCR. We estimated that human tumor-specific reads (ctDNA) or mctDNA comprised about 0.29 or 0.01%, respectively of the xenograft mouse cfDNA, and about 0.029 or 0.001% of the cfDNA of human early stage cancer patients. Similar WGBS of early stage (0-II, node- and metastasis-free) breast, lung or colorectal cancer samples identified hundreds of specific DMRs (differentially methylated regions) compared to healthy controls. Their association with tumourigenesis was supported by stage-dependent methylation, tumor suppressor or oncogene clusters, and genes also identified in the xenograft samples. Using 20 three-cancer-common and 17 colorectal cancer-specific DMRs in combination (top 0.0018% of the WGBS methylation clusters) was sufficient to distinguish the stage I colorectal cancers from breast and lung cancers and healthy controls. Our data thus confirmed the tumor origin of mctDNA by sequence specificity, and provide a selection threshold for authentic tumor mctDNA markers toward precise diagnosis of early stage cancers solely by top DMRs in combination.
- 24 samples
- DAC: EGAC00001002626
- Technology: HiSeq X Ten
Data access policy for Characterization of Cell Free Plasma Methyl-DNA From Xenografted Tumors to Guide the Selection of Diagnostic Markers for Early-Stage Cancers
Potential users should submit an institutional certificate of ethical approval to Professor Jiuyong Xie, by email to: xiej@umanitoba.ca before access to the patient data.
Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.
Study ID | Study Title | Study Type |
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EGAS00001006175 | Other |
This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.
ID | File Type | Size | Located in | |
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EGAF00006139066 | fastq.gz | 5.2 GB | ||
EGAF00006139067 | fastq.gz | 5.0 GB | ||
EGAF00006139068 | fastq.gz | 4.4 GB | ||
EGAF00006139069 | fastq.gz | 4.3 GB | ||
EGAF00006139070 | fastq.gz | 1.8 GB | ||
EGAF00006139071 | fastq.gz | 1.7 GB | ||
EGAF00006139072 | fastq.gz | 5.7 GB | ||
EGAF00006139073 | fastq.gz | 5.6 GB | ||
EGAF00006139074 | fastq.gz | 6.7 GB | ||
EGAF00006139075 | fastq.gz | 6.6 GB | ||
EGAF00006139076 | fastq.gz | 8.6 GB | ||
EGAF00006139077 | fastq.gz | 8.1 GB | ||
EGAF00006139078 | fastq.gz | 9.9 GB | ||
EGAF00006139079 | fastq.gz | 9.5 GB | ||
EGAF00006139080 | fastq.gz | 10.6 GB | ||
EGAF00006139081 | fastq.gz | 10.3 GB | ||
EGAF00006139082 | fastq.gz | 8.2 GB | ||
EGAF00006139083 | fastq.gz | 7.7 GB | ||
EGAF00006139084 | fastq.gz | 9.9 GB | ||
EGAF00006139085 | fastq.gz | 10.0 GB | ||
EGAF00006139086 | fastq.gz | 10.3 GB | ||
EGAF00006139087 | fastq.gz | 10.2 GB | ||
EGAF00006139088 | fastq.gz | 8.7 GB | ||
EGAF00006139089 | fastq.gz | 8.7 GB | ||
EGAF00006139090 | fastq.gz | 6.0 GB | ||
EGAF00006139091 | fastq.gz | 5.8 GB | ||
EGAF00006139092 | fastq.gz | 6.0 GB | ||
EGAF00006139093 | fastq.gz | 5.8 GB | ||
EGAF00006139094 | fastq.gz | 7.9 GB | ||
EGAF00006139095 | fastq.gz | 7.7 GB | ||
EGAF00006139096 | fastq.gz | 10.4 GB | ||
EGAF00006139097 | fastq.gz | 10.1 GB | ||
EGAF00006139098 | fastq.gz | 7.6 GB | ||
EGAF00006139099 | fastq.gz | 7.8 GB | ||
EGAF00006139100 | fastq.gz | 10.3 GB | ||
EGAF00006139101 | fastq.gz | 10.5 GB | ||
EGAF00006139102 | fastq.gz | 9.4 GB | ||
EGAF00006139103 | fastq.gz | 9.6 GB | ||
EGAF00006139104 | fastq.gz | 10.9 GB | ||
EGAF00006139105 | fastq.gz | 11.0 GB | ||
EGAF00006139106 | fastq.gz | 10.3 GB | ||
EGAF00006139107 | fastq.gz | 10.4 GB | ||
EGAF00006139108 | fastq.gz | 4.4 GB | ||
EGAF00006139109 | fastq.gz | 4.3 GB | ||
EGAF00006139110 | fastq.gz | 6.7 GB | ||
EGAF00006139111 | fastq.gz | 6.4 GB | ||
EGAF00006139112 | fastq.gz | 8.4 GB | ||
EGAF00006139113 | fastq.gz | 8.1 GB | ||
EGAF00006139114 | fastq.gz | 4.3 GB | ||
EGAF00006139115 | fastq.gz | 4.1 GB | ||
50 Files (381.9 GB) |