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

doi:https://doi.org/10.1038/nm.3511

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

Pathology (VUmc)

Research output: Contribution to journal › Article › Academic › peer-review

534 Citations (Scopus)

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.

Original language	English
Pages (from-to)	430-435
Number of pages	6
Journal	Nature medicine
Volume	20
Issue number	4
DOIs	https://doi.org/10.1038/nm.3511
Publication status	Published - 1 Jan 2014

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Thierry, A. R., Mouliere, F., El Messaoudi, S., Mollevi, C., Lopez-Crapez, E., Rolet, F., Gillet, B., Gongora, C., Dechelotte, P., Robert, B., Del Rio, M., Lamy, P. J., Bibeau, F., Nouaille, M., Loriot, V., Jarrousse, A. S., Molina, F., Mathonnet, M., Pezet, D., & Ychou, M. (2014). Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA. Nature medicine, 20(4), 430-435. https://doi.org/10.1038/nm.3511

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title = "Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA",

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.",

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

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doi = "https://doi.org/10.1038/nm.3511",

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Thierry, AR, Mouliere, F, El Messaoudi, S, Mollevi, C, Lopez-Crapez, E, Rolet, F, Gillet, B, Gongora, C, Dechelotte, P, Robert, B, Del Rio, M, Lamy, PJ, Bibeau, F, Nouaille, M, Loriot, V, Jarrousse, AS, Molina, F, Mathonnet, M, Pezet, D & Ychou, M 2014, 'Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA', Nature medicine, vol. 20, no. 4, pp. 430-435. https://doi.org/10.1038/nm.3511

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AU - Thierry, Alain R.

AU - Mouliere, Florent

AU - El Messaoudi, Safia

AU - Mollevi, Caroline

AU - Lopez-Crapez, Evelyne

AU - Rolet, Fanny

AU - Gillet, Brigitte

AU - Gongora, Celine

AU - Dechelotte, Pierre

AU - Robert, Bruno

AU - Del Rio, Maguy

AU - Lamy, Pierre Jean

AU - Bibeau, Frederic

AU - Nouaille, Michelle

AU - Loriot, Virginie

AU - Jarrousse, Anne Sophie

AU - Molina, Franck

AU - Mathonnet, Muriel

AU - Pezet, Denis

AU - Ychou, Marc

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

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SP - 430

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JO - Nature medicine

JF - Nature medicine

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ER -

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

Abstract

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