Clinical and therapeutic implications of BRAF mutation heterogeneity in metastatic melanoma

Nima Mesbah Ardakani, Connull Leslie, Fabienne Grieu-Iacopetta, Wei Sen Lam, Charley Budgeon, Michael Millward, Benhur Amanuel

    Research output: Contribution to journalArticle

    5 Citations (Scopus)

    Abstract

    Heterogeneity of BRAF mutation in melanoma has been a controversial subject. Quantitative data on BRAF allele frequency (AF) are sparse, and the potential relationship with response to BRAF inhibitors (BRAFi) in patients with metastatic melanoma is unknown. We quantitatively measured BRAF AF in a cohort of treatment naïve metastatic melanoma samples by pyrosequencing and correlated with survival data in patients treated with BRAFi as part of their clinical care. Fifty-two samples from 50 patients were analysed. BRAF V600E mutations were detected in 71.1% of samples followed by V600K (25%) and V600R (3.9%). There was a wide range of AF from 3.9% to 80.3% (median 41.3%). In 33 patients treated with BRAFi, there was no difference in overall or progression-free survival when the patients were categorized into high or low AF groups. There was no correlation between AF and degree of response, and no difference in survival based on genotype.

    Original languageEnglish
    Pages (from-to)233-242
    JournalPigment Cell and Melanoma Research
    Volume30
    Issue number2
    DOIs
    Publication statusPublished - 1 Mar 2017

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    Gene Frequency
    Melanoma
    Mutation
    Therapeutics
    Survival
    Disease-Free Survival
    Genotype

    Cite this

    Mesbah Ardakani, Nima ; Leslie, Connull ; Grieu-Iacopetta, Fabienne ; Lam, Wei Sen ; Budgeon, Charley ; Millward, Michael ; Amanuel, Benhur. / Clinical and therapeutic implications of BRAF mutation heterogeneity in metastatic melanoma. In: Pigment Cell and Melanoma Research. 2017 ; Vol. 30, No. 2. pp. 233-242.
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    abstract = "Heterogeneity of BRAF mutation in melanoma has been a controversial subject. Quantitative data on BRAF allele frequency (AF) are sparse, and the potential relationship with response to BRAF inhibitors (BRAFi) in patients with metastatic melanoma is unknown. We quantitatively measured BRAF AF in a cohort of treatment na{\"i}ve metastatic melanoma samples by pyrosequencing and correlated with survival data in patients treated with BRAFi as part of their clinical care. Fifty-two samples from 50 patients were analysed. BRAF V600E mutations were detected in 71.1{\%} of samples followed by V600K (25{\%}) and V600R (3.9{\%}). There was a wide range of AF from 3.9{\%} to 80.3{\%} (median 41.3{\%}). In 33 patients treated with BRAFi, there was no difference in overall or progression-free survival when the patients were categorized into high or low AF groups. There was no correlation between AF and degree of response, and no difference in survival based on genotype.",
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    Clinical and therapeutic implications of BRAF mutation heterogeneity in metastatic melanoma. / Mesbah Ardakani, Nima; Leslie, Connull; Grieu-Iacopetta, Fabienne; Lam, Wei Sen; Budgeon, Charley; Millward, Michael; Amanuel, Benhur.

    In: Pigment Cell and Melanoma Research, Vol. 30, No. 2, 01.03.2017, p. 233-242.

    Research output: Contribution to journalArticle

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    AU - Leslie, Connull

    AU - Grieu-Iacopetta, Fabienne

    AU - Lam, Wei Sen

    AU - Budgeon, Charley

    AU - Millward, Michael

    AU - Amanuel, Benhur

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