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

被引：512

作者：

Thierry, Alain R. ^{[1
,2
]}

Mouliere, Florent ^{[1
,2
]}

El Messaoudi, Safia ^{[1
,2
]}

Mollevi, Caroline ^{[3
]}

Lopez-Crapez, Evelyne ^{[4
]}

Rolet, Fanny ^{[2
]}

Gillet, Brigitte ^{[5
]}

Gongora, Celine ^{[1
]}

Dechelotte, Pierre ^{[6
]}

Robert, Bruno ^{[1
]}

Del Rio, Maguy ^{[1
]}

Lamy, Pierre-Jean ^{[4
]}

Bibeau, Frederic ^{[7
]}

Nouaille, Michelle ^{[8
]}

Loriot, Virginie ^{[9
]}

Jarrousse, Anne-Sophie ^{[6
]}

Molina, Franck ^{[2
]}

Mathonnet, Muriel ^{[8
]}

Pezet, Denis ^{[5
]}

Ychou, Marc ^{[9
]}

机构：

[1] Inst Rech Cancerol Montpellier, INSERM U896, Montpellier, France

[2] CAP DELTA, Sysdiag CNRS UMR3145, Montpellier, France

[3] Inst Canc Montpellier, Unite Biostat, Montpellier, France

[4] Inst Canc Montpellier, Lab Biol Specialisee, Montpellier, France

[5] Univ Auvergne, UMR Unite Inserm, Serv Chirurg Digest,U1071, Unite Oncol Digest,Ctr Hosp Univ Clermont Ferrand, Clermont Ferrand, France

[6] Ctr Hosp Univ Clermont Ferrand, Unite Oncol Mol, Clermont Ferrand, France

[7] Inst Canc Montpellier, Unite Biopathol, Serv Pathol, Montpellier, France

[8] Ctr Hosp Univ Limoges, Serv Chirurg Digest, Ctr Invest Clin, INSERM 0801, Limoges, France

[9] Inst Canc Montpellier, Serv Chirurg Digest, Montpellier, France

来源：

NATURE MEDICINE | 2014年 / 20卷 / 04期

关键词：

METASTATIC COLORECTAL-CANCER; K-RAS MUTATIONS; CELL-FREE DNA; ACQUIRED-RESISTANCE; PROGNOSTIC VALUE; MUTANT-DNA; CETUXIMAB; PLASMA; PROPORTION; PREDICTOR;

D O I：

10.1038/nm.3511

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：430 / +

页数：7

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