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Clinical and therapeutic implications of BRAF mutation heterogeneity in metastatic melanoma |
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| Authors: | Nima Mesbah Ardakani Connull Leslie Fabienne Grieu‐Iacopetta Wei‐Sen Lam Charley Budgeon Michael Millward Benhur Amanuel |
| Affiliation: | 1. Department of Anatomical Pathology, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Nedlands, WA, Australia;2. School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, WA, Australia;3. Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia;4. Centre for Applied Statistics, University of Western Australia, Crawley, WA, Australia;5. School of Medicine and Pharmacology, University of Western Australia, Crawley, WA, Australia |
| 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. |
| Keywords: | BRAF mutation heterogeneity allele frequency BRAF inhibitor pyrosequencing malignant melanoma |