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- Title
Clinical and pathological associations of the activating RAC1 P29S mutation in primary cutaneous melanoma.
- Authors
Mar, Victoria J.; Wong, Stephen Q.; Logan, Aleksandra; Nguyen, Trung; Cebon, Jonathan; Kelly, John W.; Wolfe, Rory; Dobrovic, Alexander; McLean, Catriona; McArthur, Grant A.
- Abstract
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 1.2 mm versus 1.6 mm, 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.
- Subjects
MUTAGENESIS; MELANOMA; ONCOGENES; REACTIVITY (Chemistry); DISEASE progression; GENETICS
- Publication
Pigment Cell & Melanoma Research, 2014, Vol 27, Issue 6, p1117
- ISSN
1755-1471
- Publication type
Article
- DOI
10.1111/pcmr.12295