Monitoring BRAF and NRAS mutations with cell-free circulating tumor DNA from metastatic melanoma patients
| Autor: | Christelle Bonnetaud, Elodie Long-Mira, Emmanuel Chamorey, Jean-Philippe Lacour, Olivier Bordone, Véronique Hofman, Catherine Butori, Coraline Bence, Henri Montaudié, Maryline Allegra, Paul Hofman, Virginie Tanga, Renaud Schiappa, Virginie Lespinet-Fabre, Florence Leduff-Blanc, Marius Ilie |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Neuroblastoma RAS viral oncogene homolog Metastatic melanoma medicine.medical_treatment Population NRAS Cell free medicine.disease_cause BRAF Targeted therapy 03 medical and health sciences 0302 clinical medicine Genotype Medicine cfDNA education neoplasms education.field_of_study Mutation business.industry 030104 developmental biology Oncology Circulating tumor DNA 030220 oncology & carcinogenesis Cancer research IDYLLA™ business Research Paper metastatic melanoma |
| Zdroj: | Scopus-Elsevier Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|