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Nat Med. 2014 Apr;20(4):430-5. doi: 10.1038/nm.3511. Epub 2014 Mar 23.

Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA.

Author information

1
1] U896 INSERM, Institut Recherche en Cancérologie de Montpellier, Montpellier, France. [2] Sysdiag UMR3145 CNRS, CAP DELTA, Montpellier, France.
2
Unité de Biostatistique, Institut du Cancer de Montpellier, Montpellier, France.
3
Laboratoire de Biologie Spécialisée, Institut du Cancer de Montpellier, Montpellier, France.
4
Sysdiag UMR3145 CNRS, CAP DELTA, Montpellier, France.
5
Centre Hospitalier Universitaire de Clermont-Ferrand, Service de Chirurgie Digestive Unité d'Oncologie Digestive, UMR Unité Inserm/Université d'Auvergne U1071, Clermont-Ferrand, France.
6
U896 INSERM, Institut Recherche en Cancérologie de Montpellier, Montpellier, France.
7
Centre Hospitalier Universitaire de Clermont-Ferrand, Anatomie Pathologique, Unité d'Oncologie moléculaire, Clermont-Ferrand, France.
8
Service de Pathologie, Unité de Biopathologie Institut du Cancer de Montpellier, Montpellier, France.
9
Centre Hospitalier Universitaire de Limoges, Service de Chirurgie Digestive, Centre d'Investigation Clinique, INSERM 0801, Limoges, France.
10
Service de Chirurgie Digestive, Institut du Cancer de Montpellier, Montpellier, France.

Abstract

Assessment of KRAS status is mandatory in patients with metastatic colorectal cancer (mCRC) before applying targeted therapy. We describe here a blinded prospective study to compare KRAS and BRAF mutation status data obtained from the analysis of tumor tissue by routine gold-standard methods and of plasma DNA using a quantitative PCR-based method specifically designed to analyze circulating cell-free DNA (cfDNA). The mutation status was determined by both methods from 106 patient samples. cfDNA analysis showed 100% specificity and sensitivity for the BRAF V600E mutation. For the seven tested KRAS point mutations, the method exhibited 98% specificity and 92% sensitivity with a concordance value of 96%. Mutation load, expressed as the proportion of mutant alleles in cfDNA, was highly variable (0.5-64.1%, median 10.5%) among mutated samples. CfDNA was detected in 100% of patients with mCRC. This study shows that liquid biopsy through cfDNA analysis could advantageously replace tumor-section analysis and expand the scope of personalized medicine for patients with cancer.

PMID:
24658074
DOI:
10.1038/nm.3511
[Indexed for MEDLINE]

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