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Published on: May 18, 2018
The molecular profile of metastatic melanoma in Australia
Megan Lyle1, Lauren E Haydu2, Alexander M Menzies3
1Melanoma Institute Australia, Sydney, NSW, Australia; The University of Sydney, Sydney, NSW, Australia; Liz Plummer Cancer Centre, Cairns, Qld, Australia.
Abstract:
Targeted therapy directed at driver oncogenic mutations offers an effective treatment option for select patients with metastatic melanoma. The aim of this study was to assess the prevalence of clinically significant somatic mutations, specifically BRAF, NRAS and KIT, in a large cohort of Australian patients with metastatic melanoma. We performed a cross-sectional cohort study of consecutive patients with American Joint Committee on Cancer (AJCC) stage IIIc unresectable or stage IV melanoma managed at Melanoma Institute Australia, and affiliated sites, that underwent molecular testing between 22 June 2009 and 19 July 2013. Additionally, we examined the change in BRAF testing methodology and patient population over time, and how this influenced the prevalence of mutations. A total of 767 molecular tests were conducted for 733 patients. BRAF V600 mutation testing was performed for 713 patients (97.2%), with an overall mutation prevalence of 37.7% (269/713); 74.3% (200/269) were the V600E genotype and 22.3% (60/269) V600K. The BRAF mutation prevalence and proportion of BRAF V600E and V600K genotypes varied across the study period, as did testing methodology and the median age of the cohorts. Of 222 patients who underwent NRAS testing, 58 (26.1%) had a mutation identified. The overall prevalence of KIT mutations was 3.7% (11/296). In Australia the prevalence of BRAF mutations is lower than initially reported, although this remains the most common mutation identified in metastatic melanoma and an important therapeutic target. NRAS mutations are more prevalent than initially described; however, other mutations reported in melanoma, including KIT, are rare in an unselected population of patients.
Insights
This study found BRAF mutations in 37.7% of Australian metastatic melanoma patients, a lower prevalence than previously thought. NRAS mutations were more common than expected, while KIT mutations were rare.
Area of Science:
- Oncology
- Genetics
- Dermatology
Background:
- Targeted therapies for metastatic melanoma rely on identifying specific driver oncogenic mutations.
- BRAF, NRAS, and KIT mutations are key targets for effective melanoma treatment.
Purpose of the Study:
- To determine the prevalence of BRAF, NRAS, and KIT mutations in Australian patients with metastatic melanoma.
- To analyze changes in BRAF testing methodology and patient demographics over time and their impact on mutation prevalence.
Main Methods:
- A cross-sectional cohort study of 733 Australian patients with AJCC stage IIIc or IV melanoma.
- Molecular testing for BRAF, NRAS, and KIT mutations conducted between June 2009 and July 2013.
- Analysis of BRAF testing methodology and patient population changes over the study period.
Main Results:
- BRAF V600 mutations were found in 37.7% of patients (V600E: 74.3%, V600K: 22.3%).
- NRAS mutations were identified in 26.1% of tested patients.
- KIT mutations were present in 3.7% of tested patients.
Conclusions:
- BRAF mutations, while the most common, show a lower prevalence in Australian metastatic melanoma patients than initially reported.
- NRAS mutations are more prevalent than previously described in this population.
- KIT mutations are rare in an unselected Australian metastatic melanoma cohort, suggesting limited utility as a primary therapeutic target in this group.
