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Updated: Apr 21, 2026
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Discordancy in BRAF mutations among primary and metastatic melanoma lesions: clinical implications for targeted
Joshua R Bradish1, Justin D Richey1, Kristin M Post1
1Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.
Abstract:
Systemic targeted molecular therapy, in the form of a selective BRAF inhibitor with or without a MEK inhibitor, is a standard treatment for patients with BRAF V600 mutation-positive melanoma with unresectable stage III and IV disease. Patients with BRAF mutation-negative primary tumors may manifest BRAF mutation-positive metastatic disease. It is unclear whether all metastatic lesions carry the same BRAF mutation status found in the primary tumor and if discordancy exists, in what frequency it occurs. Primary and matched metastatic lesions in 25 melanoma patients were tested for the BRAF V600E/Ec, V600K, V600D, and V600R mutations using a BRAF RGQ PCR kit (Qiagen). Four patients (16%) had discrepancies between their primary and metastatic melanoma BRAF status. Of these patients, 2 (8%) had BRAF mutation-positive primary melanomas with BRAF mutation-negative metastatic lesions and 2 (8%) patient had BRAF mutation-negative melanoma with a BRAF mutation-positive metastatic lesion. In summary, discordancy of BRAF mutation status is not an infrequent finding between primary and metastatic melanoma. It may be prudent in previously negative patients to determine BRAF mutation status of new metastatic tumors for proper allocation of BRAF inhibitor therapy. Discordant BRAF status may have a role in the varying patterns of response and inevitable resistance seen with BRAF inhibitor therapies.
Insights
Melanoma BRAF mutation status can differ between primary tumors and metastases. This discordancy, found in 16% of patients, impacts targeted therapy selection and treatment response for BRAF inhibitor therapies.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- Targeted molecular therapy using BRAF inhibitors is standard for BRAF V600 mutation-positive melanoma.
- The BRAF mutation status of metastatic lesions relative to the primary tumor is not fully understood.
Purpose of the Study:
- To investigate the frequency and implications of BRAF mutation status discordancy between primary and metastatic melanoma.
Main Methods:
- BRAF V600E/Ec, V600K, V600D, and V600R mutations were analyzed in primary and matched metastatic lesions from 25 melanoma patients.
- A BRAF RGQ PCR kit (Qiagen) was utilized for mutation detection.
Main Results:
- Discordant BRAF mutation status was observed in 4 out of 25 patients (16%).
- Two patients (8%) showed BRAF-positive primary tumors with BRAF-negative metastases.
- Two patients (8%) had BRAF-negative primary tumors with BRAF-positive metastases.
Conclusions:
- BRAF mutation status discordancy between primary and metastatic melanoma is a significant finding.
- Testing metastatic lesions for BRAF status in previously negative patients is crucial for appropriate BRAF inhibitor therapy allocation.
- Discordant BRAF status may influence patient response and resistance patterns to BRAF inhibitor treatments.
