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

Alain R. Thierry, Florent Mouliere, Safia El Messaoudi, Caroline Mollevi, Evelyne Lopez-Crapez, Fanny Rolet, Brigitte Gillet, Celine Gongora, Pierre Dechelotte, Bruno Robert, Maguy Del Rio, Pierre Jean Lamy, Frederic Bibeau, Michelle Nouaille, Virginie Loriot, Anne Sophie Jarrousse, Franck Molina, Muriel Mathonnet, Denis Pezet, Marc Ychou

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534 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)430-435
Number of pages6
JournalNature medicine
Issue number4
Publication statusPublished - 1 Jan 2014

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