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High fragmentation characterizes tumour-derived circulating DNA.

Published version
Peer-reviewed

Type

Article

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Authors

Robert, Bruno 
Arnau Peyrotte, Erika 
Del Rio, Maguy 
Ychou, Marc 

Abstract

BACKGROUND: Circulating DNA (ctDNA) is acknowledged as a potential diagnostic tool for various cancers including colorectal cancer, especially when considering the detection of mutations. Certainly due to lack of normalization of the experimental conditions, previous reports present many discrepancies and contradictory data on the analysis of the concentration of total ctDNA and on the proportion of tumour-derived ctDNA fragments. METHODOLOGY: In order to rigorously analyse ctDNA, we thoroughly investigated ctDNA size distribution. We used a highly specific Q-PCR assay and athymic nude mice xenografted with SW620 or HT29 human colon cancer cells, and we correlated our results by examining plasma from metastatic CRC patients. CONCLUSION/SIGNIFICANCE: Fragmentation and concentration of tumour-derived ctDNA is positively correlated with tumour weight. CtDNA quantification by Q-PCR depends on the amplified target length and is optimal for 60-100 bp fragments. Q-PCR analysis of plasma samples from xenografted mice and cancer patients showed that tumour-derived ctDNA exhibits a specific amount profile based on ctDNA size and significant higher ctDNA fragmentation. Metastatic colorectal patients (n = 12) showed nearly 5-fold higher mean ctDNA fragmentation than healthy individuals (n = 16).

Description

Keywords

Animals, Cell Line, Tumor, Colorectal Neoplasms, DNA Fragmentation, DNA, Neoplasm, Female, Health, Humans, Mice, Mice, Nude, Polymerase Chain Reaction, Tumor Burden, Xenograft Model Antitumor Assays

Journal Title

PLoS One

Conference Name

Journal ISSN

1932-6203
1932-6203

Volume Title

6

Publisher

Public Library of Science (PLoS)