Clinical and therapeutic implications of BRAF mutation heterogeneity in metastatic melanoma

Summary 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...

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Published inPigment cell and melanoma research Vol. 30; no. 2; pp. 233 - 242
Main Authors Mesbah Ardakani, Nima, Leslie, Connull, Grieu‐Iacopetta, Fabienne, Lam, Wei‐Sen, Budgeon, Charley, Millward, Michael, Amanuel, Benhur
Format Journal Article
LanguageEnglish
Published England Wiley Subscription Services, Inc 01.03.2017
Subjects
allele frequency
BRAF inhibitor
BRAF mutation
Cohort Studies
Female
Gene Frequency
Genotype
Heterogeneity
Humans
Male
malignant melanoma
Melanoma
Melanoma - drug therapy
Melanoma - genetics
Melanoma - pathology
Middle Aged
Mutation
Prognosis
Protein Kinase Inhibitors - therapeutic use
Proto-Oncogene Proteins B-raf - antagonists & inhibitors
Proto-Oncogene Proteins B-raf - genetics
pyrosequencing
Skin Neoplasms - drug therapy
Skin Neoplasms - genetics
Skin Neoplasms - pathology
BRAF inhibitor
pyrosequencing
malignant melanoma
heterogeneity
BRAF mutation
allele frequency
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Summary:Summary 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.
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ISSN:1755-1471
1755-148X
DOI:10.1111/pcmr.12569