Quantitative characterization of tumor cell-free DNA shortening.

BMC Genomics
Juntang GuoJin Huang

Abstract

Previous studies found that cell-free DNA (cfDNA) generated from tumors was shorter than that from healthy cells, and selecting short cfDNA could enrich for tumor cfDNA and improve its usage in early cancer diagnosis and treatment monitoring; however, the underlying mechanism of shortened tumor cfDNA was still unknown, which potentially limits its further clinical application. Using targeted sequencing of cfDNA in a large cohort of solid tumor patient, sequencing reads harboring tumor-specific somatic mutations were isolated to examine the exact size distribution of tumor cfDNA. For the majority of studied cases, 166 bp remained as the peak size of tumor cfDNA, with tumor cfDNA showing an increased proportion of short fragments (100-150 bp). Less than 1% of cfDNA samples were found to be peaked at 134/144 bp and independent of tumor cfDNA purity. Using whole-genome sequencing of cfDNA, we discovered a positive correlation between cfDNA shortening and the magnitude of chromatin inaccessibility, as measured by transcription, DNase I hypersensitivity, and histone modifications. Tumor cfDNA shortening occurred simultaneously at both 5' and 3' ends of the DNA wrapped around nucleosomes. Tumor cfDNA shortening exhibited two distincti...Continue Reading

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Datasets Mentioned

BETA
SRX1921680
GM12878

Methods Mentioned

BETA
xenografts
biopsy
ChIP-seq
xenograft
RNA-Seq

Software Mentioned

ABSOLUTE
COSMIC
VarScan
Trimmomatics Aligner
Genome Analysis Toolkit
- mem )
LOWESS
FANTOM5

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