Related Experiment Video
Updated: Aug 13, 2026
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Examination of mutations in BRAF, NRAS, and PTEN in primary cutaneous melanoma
Vikas K Goel1, Alexander J F Lazar, Carla L Warneke
1Department of Medicine, Division of Hematology/Oncology, Massachusetts General Hospital, Melanoma Center, Boston, Massachusetts, USA.
Abstract:
Frequent somatic mutation of v-raf murine sarcoma viral oncogene homolog B (BRAF), a downstream effector of the rat sarcoma oncogene (RAS) signaling pathway, is described in melanoma and other tumors. Our analysis of melanoma cell lines suggests that activating mutations in BRAF can occur simultaneously with inactivation of phosphatase and tensin homolog (PTEN), but neuroblastoma RAS (NRAS) mutations are not coincident. We determined the concurrent prevalence of mutations in BRAF and NRAS, and alteration of PTEN expression in 69 primary cutaneous melanomas. BRAF mutations were seen in 57% of cases. NRAS was mutated in 17% of samples, exclusively in exon 2. Two cases showed concurrent BRAF and NRAS mutations. Using immunohistochemistry, PTEN protein expression was lost or greatly reduced in 19% of tumors. Seven tumors with reduced PTEN yielded DNA amenable to sequencing, and three also showed mutation in BRAF but none in NRAS. In all, 11 (85%) of 13 tumors showing reduced PTEN expression were greater than 3.5 mm thick, and the association of increasing Breslow thickness and loss or reduction of PTEN expression was statistically significant (P<0.0001). Mutations in NRAS were not coincident with reduced PTEN expression, and the concurrent mutation of NRAS and BRAF was rare.
Insights
Activating BRAF mutations are common in melanoma. Loss of PTEN expression is linked to thicker tumors, but not NRAS mutations, suggesting distinct roles in melanoma progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Somatic mutations in BRAF (v-raf murine sarcoma viral oncogene homolog B) are frequent in melanoma.
- BRAF is a key effector in the RAS (rat sarcoma oncogene) signaling pathway.
- Investigating co-occurring mutations and expression alterations provides insight into melanoma pathogenesis.
Purpose of the Study:
- To determine the concurrent prevalence of BRAF and NRAS mutations and PTEN expression alterations in primary cutaneous melanomas.
- To explore the relationship between these genetic alterations and tumor thickness.
Main Methods:
- Analysis of BRAF and NRAS mutations via DNA sequencing.
- Assessment of PTEN protein expression using immunohistochemistry.
- Correlation of genetic findings with clinical data, including Breslow thickness.
Main Results:
- BRAF mutations occurred in 57% of melanomas, while NRAS mutations were found in 17%, exclusively in exon 2.
- Loss or significant reduction of PTEN expression was observed in 19% of tumors.
- Reduced PTEN expression was strongly associated with increased tumor thickness (P<0.0001).
- Concurrent BRAF and NRAS mutations were rare, and NRAS mutations did not coincide with reduced PTEN expression.
Conclusions:
- BRAF mutations are prevalent in cutaneous melanoma.
- Loss of PTEN expression is a significant indicator of advanced tumor thickness.
- NRAS mutations and PTEN inactivation appear to be largely independent events in melanoma progression.
Related Concept Videos
01:30Skin Cancer
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
02:38The Ras Gene
Ras is a superfamily...