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

A.R. Thierry; F. Mouliere; S. El Messaoudi; C. Mollevi; E. Lopez-Crapez; F. Rolet; B. Gillet; C. Gongora; P. Dechelotte; B. Robert; M. Del Rio; P.-J. Lamy; F. Bibeau; M. Nouaille; V. Loriot; A.-S. Jarrousse; F. Molina; M. Mathonnet; D. Pezet; M. Ychou

doi:10.1038/nm.3511

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

A.R. Thierry^*, F. Mouliere, S. El Messaoudi, C. Mollevi, E. Lopez-Crapez, F. Rolet, B. Gillet, C. Gongora, P. Dechelotte, B. Robert, M. Del Rio, P.-J. Lamy, F. Bibeau, M. Nouaille, V. Loriot, A.-S. Jarrousse, F. Molina, M. Mathonnet, D. Pezet, M. Ychou

^*Corresponding author for this work

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

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 - 23 Mar 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 = "A.R. Thierry and F. Mouliere and {El Messaoudi}, S. and C. Mollevi and E. Lopez-Crapez and F. Rolet and B. Gillet and C. Gongora and P. Dechelotte and B. Robert and {Del Rio}, M. and P.-J. Lamy and F. Bibeau and M. Nouaille and V. Loriot and A.-S. Jarrousse and F. Molina and M. Mathonnet and D. Pezet and M. Ychou",

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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, 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, vol. 20, no. 4, pp. 430–435. https://doi.org/10.1038/nm.3511

TY - JOUR

T1 - Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA

AU - Thierry, A.R.

AU - Mouliere, F.

AU - El Messaoudi, S.

AU - Mollevi, C.

AU - Lopez-Crapez, E.

AU - Rolet, F.

AU - Gillet, B.

AU - Gongora, C.

AU - Dechelotte, P.

AU - Robert, B.

AU - Del Rio, M.

AU - Lamy, P.-J.

AU - Bibeau, F.

AU - Nouaille, M.

AU - Loriot, V.

AU - Jarrousse, A.-S.

AU - Molina, F.

AU - Mathonnet, M.

AU - Pezet, D.

AU - Ychou, M.

PY - 2014/3/23

Y1 - 2014/3/23

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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VL - 20

SP - 430

EP - 435

JO - Nature Medicine

JF - Nature Medicine

IS - 4

ER -

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

Abstract

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