title: BRAF analysis on a spectrum of melanocytic neoplasms: an epidemiological study across differing UV regions.
abstract: BRAF mutation has been linked to the development of melanocytic tumors in homogeneous Caucasian cohorts. The role of solar UV radiation (UVR) in BRAF mutation status is poorly understood. We studied the epidemiology of BRAF mutation across a spectrum of melanocytic neoplasms in populations with differing UVR rates. Extended testing for 9 mutation types was attempted on 600 melanocytic neoplasms including banal nevi (n = 225), dysplastic nevi (n = 113), primary (n = 172), and metastatic melanomas (n = 90). Specimens were collected from 4 countries with increasing UVR rates (in kJ/m/yr): Syria (n = 45; UVR = 93.5), Lebanon (n = 225; UVR = 110), Pakistan (n = 122; UVR = 128), and Saudi Arabia (n = 208; UVR = 139). UVR was estimated from 21-year averages from The National Center for Atmospheric Research database. The overall BRAF mutation rate was 49% (268 of 545) and differed significantly by the geographic location [34% Pakistan, 49% Lebanon, 67% Syria, and 54% Saudi Arabia; P = 0.001], neoplasm type (P < 0.001), and anatomical location (P < 0.001) but not with age (P = 0.07) and gender (P = 1.0). V600E was the predominant mutation type, found in 96.3% of the cases. Incidence of melanoma was significantly greater in BRAF-negative (39%) versus BRAF-positive (17%) groups. For BRAF-positive cases, less severe lesions were systematically more frequent (P < 0.001). Multivariate analysis indicated that BRAF mutation is predicted by neoplasm type, anatomical site, and geographic location. In our Near East cohort, BRAF mutation rates varied by geographic location but not based on UVR. BRAF-positive status was associated with less severe lesions.
authors.affiliation: *Department of Pathology, American University of Beirut Medical Center, Beirut, Lebanon; †Department of Internal Medicine, Outcomes Research Unit, American University of Beirut Medical Center, Beirut, Lebanon; ‡Department of Pathology, Saad Specialist Hospital, Al Khobar, Kingdom of Saudi Arabia; §Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan; ¶Department of Pathology, Tishreen University, Lattakia, Syrian Arab Republic; ‖Department of Pathology, Dhahran Health Center, Dhahran, Kingdom of Saudi Arabia; **Department of Pathology, King Fahd Specialist Hospital, Dammam, Kingdom of Saudi Arabia; ††Department of Pathology, King Abdul-Aziz Medical City, Jeddah, Kingdom of Saudi Arabia; and ‡‡ViennaLab Diagnostics GmbH, Vienna, Austria.
authors.forename: Maya
authors.initials: M
authors.lastname: Saroufim
authors.forename: Robert
authors.initials: R
authors.lastname: Habib
authors.forename: Sarah
authors.initials: S
authors.lastname: Karram
authors.forename: Cleo
authors.initials: C
authors.lastname: Youssef Massad
authors.forename: Suad
authors.initials: S
authors.lastname: Taraif
authors.forename: Asif
authors.initials: A
authors.lastname: Loya
authors.forename: Mohammad Adib
authors.initials: MA
authors.lastname: Houreih
authors.forename: Salwa S
authors.initials: SS
authors.lastname: Sheikh
authors.forename: Samir S
authors.initials: SS
authors.lastname: Amr
authors.forename: Mohamed
authors.initials: M
authors.lastname: Satti
authors.forename: Christian
authors.initials: C
authors.lastname: Oberkanins
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Khalifeh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008545:Melanoma / Q000453:epidemiology* / Q000235:genetics*; D008875:Middle Aged; D009506:Nevus / Q000235:genetics / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D013472:Sunlight / Q000009:adverse effects; D014466:Ultraviolet Rays; D055815:Young Adult
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf