Clinical and pathological associations of the activating RAC1 P29S mutation in primary cutaneous melanoma
A partir d'échantillons tumoraux prélevés sur 814 patients atteints d'un mélanome cutané primitif, cette étude suggère que la présence d'une mutation activatrice du gène RAC favorise la progression des mélanomes présentant un gène BRAF muté
Activating mutations in the GTPase RAC1 are a recurrent event in cutaneous melanoma. We investigated the clinical and pathological associations of RAC1P29S in a cohort of 814 primary cutaneous melanomas with known BRAF and NRAS mutation status. The RAC1P29S mutation had a prevalence of 3.3% and was associated with increased thickness (OR=1.6 p=0.001), increased mitotic rate (OR=1.3 p=0.03), ulceration (OR=2.4 p=0.04), nodular subtype (OR=3.4 p=0.004) and nodal disease at diagnosis (OR=3.3 p=0.006). BRAF mutant tumors were also associated with nodal metastases (OR=1.9 p=0.004), despite being thinner at diagnosis than BRAF WT (median 1.2mm versus 1.6mm, p<0.001). Immunohistochemical analysis of 51 melanomas revealed that 47% were immunoreactive for RAC1. Melanomas were more likely to show RAC1 immunoreactivity if they were BRAF mutant (OR=5.2 p=0.01). RAC1 may therefore be important in regulating the early migration of BRAF mutant tumors. RAC1 mutations are infrequent in primary melanomas but may accelerate disease progression.