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Cited by 243

The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.

Quantitative Cell-Free Circulating BRAFV600E Mutation Analysis by Use of Droplet Digital PCR in the Follow-up of Patients with Melanoma Being Treated with BRAF Inhibitors

Sanmamed, Miguel F, Fernández-Landázuri, Sara, Rodríguez, Carmen, Zárate, Ruth, Lozano, María D, Zubiri, Leyre, Perez-Gracia, José Luis, Martín-Algarra, Salvador, González, Alvaro·2015·Clinical Chemistry

Abstract

BACKGROUND: Around 50% of cutaneous melanomas harbor the BRAFV600E mutation and can be treated with BRAF inhibitors. DNA carrying this mutation can be released into circulation as cell-free BRAFV600E (cfBRAFV600E). Droplet digital PCR (ddPCR) is an analytically sensitive technique for quantifying small concentrations of DNA. We studied the plasma concentrations of cfBRAFV600E by ddPCR in patients with melanoma during therapy with BRAF inhibitors. METHODS: Plasma concentrations of cfBRAFV600E were measured in 8 controls and 20 patients with advanced melanoma having the BRAFV600E mutation during treatment with BRAF inhibitors at baseline, first month, best response, and progression. RESULTS: The BRAFV600E mutation was detected by ddPCR even at a fractional abundance of 0.005% in the wild-type gene. Agreement between tumor tissue BRAFV600E and plasma cfBRAFV600E was 84.3%. Baseline cfBRAFV600E correlated with tumor burden (r = 0.742, P < 0.001). cfBRAFV600E concentrations decreased significantly at the first month of therapy (basal median, 216 copies/mL; Q1–Q3, 27–647 copies/mL; first response median, 0 copies/mL; Q1–Q3, 0–49 copies/mL; P < 0.01) and at the moment of best response (median, 0 copies/mL; Q1–Q3, 0–33 copies/mL; P < 0.01). At progression, there was a significant increase in the concentration of cfBRAFV600E compared with best response (median, 115 copies/mL; Q1–Q3, 3–707 copies/mL; P = 0.013). Lower concentrations of basal cfBRAFV600E were significantly associated with longer overall survival and progression-free survival (27.7 months and 9 months, respectively) than higher basal concentrations (8.6 months and 3 months, P < 0.001 and P = 0.024, respectively). CONCLUSIONS: cfBRAFV600E quantification in plasma by ddPCR is useful as a follow-up to treatment response in patients with advanced melanoma.

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Metadata

Authors
Sanmamed, M. F., Fernández-Landázuri, S., Rodríguez, C., Zárate, R., Lozano, M. D., Zubiri, L., Perez-Gracia, J. L., Martín-Algarra, S., & González, A.
Venue
Clinical Chemistry
Published
2015-01-01
Volume
61
Issue
1
Pages
297-304
ISSN
  • 0009-9147 (ISSN-L)
  • 1530-8561
OpenAlex
W2169198176
Cited by
243
References
9
FWCI
8.76
Type
journal article
Language
en
Open access
closed

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Sanmamed, M. F., Fernández-Landázuri, S., Rodríguez, C., Zárate, R., Lozano, M. D., Zubiri, L., Perez-Gracia, J. L., Martín-Algarra, S., & González, A. (2015). Quantitative Cell-Free Circulating BRAFV600E Mutation Analysis by Use of Droplet Digital PCR in the Follow-up of Patients with Melanoma Being Treated with BRAF Inhibitors. Clinical Chemistry. https://doi.org/10.1373/clinchem.2014.230235

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