Association between BRAF
V600E and NRAS
Q61R mutations and clinicopathologic characteristics,risk factors and clinical outcome of primary invasive cutaneous melanoma |
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Authors: | Shaowei Wu Helen Kuo Wen-Qing Li Alvaro Laga Canales Jiali Han Abrar A Qureshi |
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Institution: | 1. Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA 2. Department of Dermatology, Warren Alpert Medical School, Brown University, 339 Eddy Street, Providence, RI, 02903, USA 3. Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA 4. Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA 5. Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA 6. Department of Dermatology, School of Medicine, Indiana University, Indianapolis, IN, USA 7. Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
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Abstract: | Purpose Previous studies suggest that solar UV exposure in early life is predictive of cutaneous melanoma risk in adulthood, whereas the relation of BRAF mutation with sun exposure and disease prognosis has been less certain. We investigated the associations between BRAFV600E and NRASQ61R mutations and known risk factors, clinicopathologic characteristics and clinical outcomes of melanoma in a case series of primary invasive cutaneous melanoma from the Nurses’ Health Study (NHS). Methods Somatic BRAFV600E and NRASQ61R mutations of 127 primary invasive melanomas from the NHS cohort were determined by pyrosequencing using formalin-fixed, paraffin-embedded block tissues. Logistic regression analyses were performed to detect the associations of mutations with melanoma risk factors, and Kaplan–Meier method was used to examine associations between mutations and survival. Results The odds ratios for harboring BRAFV600E mutations were 5.54 (95 % CI 1.19–25.8, p trend = 0.02) for women residing in states with UV index ≥ 7 versus those residing in states with UV index ≤5 at 30 years of age. Patients with BRAFV600E mutations tended to have shorter melanoma-specific survival when compared to patients with wild type at both loci (median survival time 110 vs. 159 months) (p = 0.03). No association was found between NRASQ61R mutation and melanoma risk factors or melanoma-specific survival. Conclusions BRAFV600E mutations in primary cutaneous melanomas were associated with residence in locations with medium and high UV indices in mid-life. BRAFV600E mutation may be associated with an unfavorable prognosis among melanoma patients. |
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