Clinical and pathological associations of the activating RAC1 P29S mutation in primary cutaneous melanoma. (4th August 2014)

• Record Type: Journal Article
• 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.
• Is Part Of: Pigment cell & melanoma research. Volume 27:Number 6(2014:Nov.)
• Page Start: 1117
• Page End: 1125
• Publication Date: 2014-08-04
• Subjects: Melanoma -- Periodicals; Chromatophores -- Periodicals; Animal pigments -- Periodicals; 616.99477
• DOI: 10.1111/pcmr.12295
• Languages: English
• ISSNs: 1755-1471

Abstract

<abstract abstract-type="main" id="pcmr12295-abs-0001"> <title>Summary</title> <p>Activating mutations in the GTPase <italic>RAC1</italic> are a recurrent event in cutaneous melanoma. We investigated the clinical and pathological associations of <italic>RAC1</italic>^P29S in a cohort of 814 primary cutaneous melanomas with known <italic>BRAF</italic> and <italic>NRAS</italic> mutation status. The <italic>RAC1</italic>^P29S 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). <italic>BRAF</italic> mutant tumors were also associated with nodal metastases (OR=1.9 P = 0.004), despite being thinner at diagnosis than <italic>BRAF</italic> WT (median 1.2 mm versus 1.6 mm, P &lt; 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 <italic>BRAF</italic> mutant (OR=5.2 P = 0.01). <italic>RAC1</italic> may therefore be important in regulating the early migration of <italic>BRAF</italic> mutant tumors. <italic>RAC1</italic> mutations are infrequent in primary melanomas but may accelerate disease progression.</p> </abstract>