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Updated: Aug 25, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Incidence of BRAF oncogene mutation and clinical relevance for primary cutaneous melanomas
Masaru Shinozaki1, Akihide Fujimoto, Donald L Morton
1Department Molecular Oncology, Saint John's Health Center, Santa Monica, California 90404, USA.
Purpose:
The purpose of the study was to clarify the incidence of B-raf oncogene (BRAF) mutations in primary cutaneous melanomas, their relation to tumor progression, and effect on disease outcome. Somatic mutations of BRAF kinase, a component of the Ras-mitogen-activated protein/extracellular signal-regulated kinase kinase-mitogen-activated protein kinase pathway, are frequently reported (>65%) in nevi and malignant melanomas.
Experimental Design:
We assessed BRAF mutation frequency in exons 11 and 15 in primary (n = 59) and metastatic (n = 68) melanomas. Direct sequencing of PCR products was performed on DNA isolated and purified from microdissected tumors.
Results:
Eighteen mutations (31%) at exon 15 were detected in primary melanoma with a significantly (P = 0.001) higher frequency in patients < 60 years old. Incidence of BRAF mutation did not correlate with Breslow thickness. Presence of BRAF mutation of primary tumors did not effect overall disease-free survival. BRAF mutation frequency in metastatic lesions was 57% and significantly (P = 0.0024) higher than primary melanomas.
Conclusions:
The study suggests that BRAF mutation may be acquired during development of metastasis but is not a significant factor for primary tumor development and disease outcome.
Insights
BRAF mutations are common in melanoma, particularly in metastatic lesions. These mutations do not significantly impact primary tumor development or patient survival outcomes.
Area of Science:
- Oncology
- Genetics
- Dermatology
Background:
- Somatic mutations in the B-raf oncogene (BRAF) kinase are frequently observed in nevi and malignant melanomas.
- BRAF mutations are a key component of the Ras-mitogen-activated protein/extracellular signal-regulated kinase kinase-mitogen-activated protein kinase pathway.
Purpose of the Study:
- To determine the incidence of BRAF mutations in primary cutaneous melanomas.
- To investigate the relationship between BRAF mutations and tumor progression.
- To assess the impact of BRAF mutations on disease outcome.
Main Methods:
- BRAF mutation frequency was assessed in exons 11 and 15 of primary (n=59) and metastatic (n=68) melanomas.
- DNA was isolated from microdissected tumors, and direct sequencing of PCR products was performed.
Main Results:
- BRAF mutations were detected in 31% of primary melanomas, with a higher frequency in patients under 60.
- BRAF mutation incidence did not correlate with Breslow thickness in primary tumors.
- BRAF mutation frequency was significantly higher in metastatic lesions (57%) compared to primary melanomas.
Conclusions:
- BRAF mutations may be acquired during melanoma metastasis.
- BRAF mutations are not a significant factor in primary tumor development.
- BRAF mutations do not appear to significantly affect overall disease-free survival.
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