title: Association between BRAFV600E and NRASQ61R mutations and clinicopathologic characteristics, risk factors and clinical outcome of primary invasive cutaneous melanoma.
abstract: OBJECTIVE
  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 BRAF(V600E) and NRAS(Q61R) 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 BRAF(V600E) and NRAS(Q61R) 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 BRAF(V600E) 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 BRAF(V600E) 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
  BRAF(V600E) mutations in primary cutaneous melanomas were associated with residence in locations with medium and high UV indices in mid-life. BRAF(V600E) mutation may be associated with an unfavorable prognosis among melanoma patients.
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Shaowei
authors.initials: S
authors.lastname: Wu
authors.forename: Helen
authors.initials: H
authors.lastname: Kuo
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Li
authors.forename: Alvaro Laga
authors.initials: AL
authors.lastname: Canales
authors.forename: Jiali
authors.initials: J
authors.lastname: Han
authors.forename: Abrar A
authors.initials: AA
authors.lastname: Qureshi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D011379:Prognosis; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012307:Risk Factors; D012878:Skin Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D015996:Survival Rate; D016896:Treatment Outcome; D014466:Ultraviolet Rays / Q000009:adverse effects; D000096142:Cutaneous Malignant Melanoma
chemical_list: D008565:Membrane Proteins; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human