Circulating free DNA as biomarker and source for mutation detection in metastatic colorectal cancer

Circulating cell-free DNA (cfDNA) in plasma has shown potential as biomarker in various cancers and could become an importance source for tumour mutation detection. The objectives of our study were to establish a normal range of cfDNA in a cohort of healthy individuals and to compare this with four...

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Bibliographic Details
Published in:PloS one 2015-04, Vol.10 (4), p.e0108247-e0108247
Main Authors: Spindler, Karen Lise Garm, Pallisgaard, Niels, Andersen, Rikke Fredslund, Brandslund, Ivan, Jakobsen, Anders
Format: Article
Language:English
Subjects:
Adult
Aged
Alleles
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biomarkers
Biomarkers, Tumor - blood
Biomarkers, Tumor - genetics
Cancer
Cancer genetics
Cancer metastasis
Chemotherapy
Clinical trials
Colon - drug effects
Colon - pathology
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - blood
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
Deoxyribonucleic acid
DNA
DNA - blood
DNA - genetics
Ethylenediaminetetraacetic acids
Female
Gene mutation
Genetic aspects
Humans
K-Ras protein
Male
Metastases
Middle Aged
Multivariate analysis
Mutation
Neoplasm Metastasis - drug therapy
Neoplasm Metastasis - genetics
Neoplasm Metastasis - pathology
Patients
Prognosis
Prospective Studies
Proto-Oncogene Proteins p21(ras) - genetics
Quartiles
Rectum - drug effects
Rectum - pathology
Tumors
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Summary:Circulating cell-free DNA (cfDNA) in plasma has shown potential as biomarker in various cancers and could become an importance source for tumour mutation detection. The objectives of our study were to establish a normal range of cfDNA in a cohort of healthy individuals and to compare this with four cohorts of metastatic colorectal cancer (mCRC) patients. We also investigated the prognostic value of cfDNA and analysed the tumour-specific KRAS mutations in the plasma. The study was a prospective biomarker evaluation in four consecutive Phase II trials, including 229 patients with chemotherapy refractory mCRC and 100 healthy individuals. Plasma was obtained from an EDTA blood-sample, and the total number of DNA alleles and KRAS mutated alleles were assessed using an in-house ARMS-qPCR as previously described. Median cfDNA levels were higher in mCRC compared to controls (p < 0.0001). ROC analysis revealed an AUC of 0.9486 (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0108247