Monitoring BRAF and NRAS mutations with cell-free circulating tumor DNA from metastatic melanoma patients.
Oncotarget
; 9(90): 36238-36249, 2018 Nov 16.
Article
em En
| MEDLINE
| ID: mdl-30546839
ABSTRACT
The mutation status of the BRAF and NRAS genes in tumor tissue is used to select patients with metastatic melanoma for targeted therapy. Cell-free circulating DNA (cfDNA) represents an accessible, non-invasive surrogate sample that could provide a snapshot of the BRAF and NRAS genotype in these patients. We investigated the feasibility of the Idylla™ assay for detection of BRAF and NRAS mutations in cfDNA of 19 patients with metastatic melanoma at baseline and during the course of treatment. The cfDNA genotype obtained with Idylla was compared to the results obtained with matched-tumor tissue and to clinical outcome. At baseline, 47% of patients harbored a BRAFV600 mutation in their cfDNA. Two months after targeted treatment the BRAFV600 mutant cfDNA was undetectable in all patients and 3 were disease-free. Moreover, 15% of patients harbored a NRAS mutation that was detected with plasma before treatment. The sensitivity and specificity were 80% and 89% for the BRAF status, and 79% and 100% for the NRAS status in pretreatment cfDNA compared to results obtained with a tissue test. Due to the small size of the population, no significant correlation was observed between the presence of BRAF or NRAS mutations in cfDNA and the metastatic tumor load or overall survival. In conclusion, this study demonstrated that evaluation with the Idylla system of the BRAF and NRAS mutation status in cfDNA may be a surrogate for determination of the BRAF and NRAS status in tumor tissue.
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01-internacional
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MEDLINE
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article