|
|||||
|
|
Clinical and pathological associations of the activating RAC1 P29S mutation in primary cutaneous melanoma |
|
| Authors: | Victoria J Mar Stephen Q Wong Aleksandra Logan Trung Nguyen Jonathan Cebon John W Kelly Rory Wolfe Alexander Dobrovic Catriona McLean Grant A McArthur |
| Institution: | 1. Victorian Melanoma Service, Alfred Hospital, , Melbourne, Vic., Australia;2. Department of Epidemiology and Preventive Medicine, Monash University, , Melbourne, Vic., Australia;3. Sir Peter MacCallum Department of Oncology, The University of Melbourne, , Parkville, Vic., Australia;4. Translational Research Laboratory, Cancer Therapeutics Program, Peter MacCallum Cancer Centre, , East Melbourne, Vic., Australia;5. Molecular Pathology, Peter MacCallum Cancer Centre, , East Melbourne, Vic., Australia;6. Department of Pathology, Alfred Hospital, , Melbourne, Vic., Australia;7. Translational Genomics and Epigenomics Laboratory, Ludwig Institute for Cancer Research, Olivia Newton‐John Cancer and Wellness Centre, , Heidelberg, Vic., Australia;8. Department of Pathology, University of Melbourne, , Parkville, Vic., Australia;9. Molecular Oncology Laboratory, Oncolgenic Signaling and Growth Control Program, Peter MacCallum Cancer Centre, , East Melbourne, Vic., Australia;10. Molecular Imaging and Targeted Therapeutics Laboratory, Cancer Therapeutics Program, Peter MacCallum Cancer Centre, , East Melbourne, Vic., Australia;11. Department of Medicine, St. Vincent's Hospital, University of Melbourne, , Fitzroy, Vic., Australia;12. Department of Cancer Imaging, Peter MacCallum Cancer Centre, , East Melbourne, Vic., Australia |
| 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. |
| Keywords: | RAC1 mutation RAC1 immunoreactivity RAC1 expression melanoma metastasis melanoma progression BRAF |