BRAF V600E Mutations in Nevi and Melanocytic Tumors of Uncertain Malignant Potential

Cells to Surgery Quiz: June 2019

“…It has, therefore, been postulated that the BRAF V600E mutation by itself is not oncogenic but allows for melanocytic hyperplasia and that within that milieu, additional key oncogenic mutations can take place (Poynter et al, 2006;Shain and Bastian, 2016;Shain et al, 2015). Seitz-Alghrouz et al report results from their study similar to those already in the literature, identifying a lower rate of BRAF V600E mutations in MELTUMPs compared with benign nevi (Seitz-Alghrouz et al, 2018). Their findings are compatible with the idea that the BRAF V600E mutation is common in benign nevi and is an important mutagenic event leading to melanocytic proliferation with the potential for malignant conversion after additional key mutations.…”

“…Older age and female sex were associated with a more significant percentage of BRAF mutations in benign nevi and MELTUMPs. Seitz-Alghrouz et al (2018) report that the age of BRAF V600E-positive MELTUMP patients (46.3 years) was younger than the age of MELTUMP patients with wild-type BRAF (52 years), although this finding was not statistically significant. Additionally, the authors identified sexdependent differences with the BRAF V600E mutation rate, because it was significantly more often located in nevi of males than females.…”

“…The common BRAF V600E mutation typically results from a T>A transversion, rather than the classic C>T transition that is the hallmark of UV-induced mutagenesis (Shain and Bastian, 2016). Seitz-Alghrouz et al (2018) also identified this finding in their data, specifically in MELTUMPs, with the trunk being the most common site of the lesions with BRAF V600E mutations. This finding is in accordance with many previous studies involving MM and benign nevi (Poynter et al, 2006;Shain et al, 2015;Uribe et al, 2003).…”

“…Seitz-Alghrouz et al (2018) sought to better define BRAF V600E mutation rates in benign nevi and MELTUMPs in 85 total specimens. They found that 70% (28/40) of the benign nevi harbored BRAF V600E mutations but that only 51% (23/ 45) of the MELTUMPs had the mutation, although this finding was not statistically significant (Seitz-Alghrouz et al, 2018). The BRAF V600E mutation is a common finding in benign nevi; zebrafish models have shown this mutation to be a sufficient event to lead to nevogenesis (Shain and Bastian, 2016).…”

“…3. According to Seitz-Alghrouz et al (2018), the significance of the BRAF mutation in their study can be best described by which statement?…”