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Updated: Jun 24, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Oncogenic Braf induces melanocyte senescence and melanoma in mice
Nathalie Dhomen1, Jorge S Reis-Filho, Silvy da Rocha Dias
1Signal Transduction Team, Cancer Research UK Centre for Cell and Molecular Biology, The Institute of Cancer Research, London, UK.
Abstract:
We show here that inducible expression of Braf(V600E) off the endogenous Braf gene in mouse melanocytes stimulates skin hyperpigmentation and the appearance of nevi harboring senescent melanocytes. Additionally, approximately 70% of Braf(V600E) mice develop melanomas that reproduce many of the cardinal histological and molecular features of human melanoma and whose cells can colonize the lungs of nude mice. We show that the tumor suppressor p16(INK4a) is not required to induce melanocyte senescence and that its loss is not required for tumor progression, although it does regulate tumor penetrance and latency. Thus, we have developed a mouse model of melanoma driven by Braf(V600E) expressed at physiological levels that reflects the genetics and pathology of the human disease.
Insights
Inducible Braf(V600E) expression in mice causes skin hyperpigmentation and melanoma. This new mouse model accurately reflects human melanoma genetics and pathology, aiding further research.
Area of Science:
- Oncology
- Dermatology
- Genetics
Background:
- The BRAF V600E mutation is a key driver in melanoma development.
- Existing mouse models often do not fully recapitulate human melanoma's complexity.
Purpose of the Study:
- To develop a novel mouse model for studying melanoma driven by Braf(V600E) at physiological levels.
- To investigate the role of Braf(V600E) in melanoma initiation, progression, and senescence.
Main Methods:
- Inducible expression of Braf(V600E) in endogenous Braf gene in mouse melanocytes.
- Histological and molecular analysis of skin lesions and tumors.
- Assessment of tumor cell colonization in nude mice.
Main Results:
- Braf(V600E) expression induced skin hyperpigmentation, nevi with senescent melanocytes, and melanoma in approximately 70% of mice.
- The developed melanomas mirrored key features of human melanoma.
- Tumor suppressor p16(INK4a) was not essential for senescence induction or tumor progression but influenced latency and penetrance.
Conclusions:
- A Braf(V600E)-driven mouse model accurately reflects human melanoma pathology and genetics.
- This model provides a valuable tool for understanding melanoma development and testing therapeutic strategies.
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