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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.

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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
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
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)