title: Distinct clinical and pathological features are associated with the BRAF(T1799A(V600E)) mutation in primary melanoma.
abstract: The BRAF(T1799A) mutation encodes BRAF(V600E) that leads to activation of the mitogen-activated protein kinase pathway. This study aimed to assess the clinico-pathological features of primary invasive melanomas containing the BRAF(T1799A) mutation. Patients (n=251) with invasive primary melanomas from Australia were interviewed and examined with respect to their melanoma characteristics and risk factors. Independent review of pathology, allele-specific PCR for the BRAF(T1799A) mutation, immunohistochemical staining with Ki67, and phospho-histone-H3 (PH3) were performed. The BRAF(T1799A) mutation was found in 112 (45%) of the primary melanomas. Associations with the BRAF(T1799A) mutation (P<0.05) were as follows: low tumor thickness (odds ratio (OR)=3.3); low mitotic rate (OR=2.0); low Ki67 score (OR=5.0); low PH3 score (OR=3.3); superficial spreading melanoma (OR=10.0); pigmented melanoma (OR=3.7); a lack of history of solar keratoses (OR=2.7); a location on the trunk (OR=3.4) or extremity (OR=2.0); a high level of self-reported childhood sun exposure (OR=2.0); < or =50 years of age (OR=2.5); and fewer freckles (OR=2.5). We conclude that the BRAF(T1799A) mutation has associations with host phenotype, tumor location, and pigmentation. Although implicated in the control of the cell cycle, the BRAF(T1799A) mutation is associated with a lower rate of tumor proliferation.
authors.affiliation: Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
authors.forename: Wendy
authors.initials: W
authors.lastname: Liu
authors.forename: John W
authors.initials: JW
authors.lastname: Kelly
authors.forename: Melanie
authors.initials: M
authors.lastname: Trivett
authors.forename: William K
authors.initials: WK
authors.lastname: Murray
authors.forename: John P
authors.initials: JP
authors.lastname: Dowling
authors.forename: Rory
authors.initials: R
authors.lastname: Wolfe
authors.forename: Graham
authors.initials: G
authors.lastname: Mason
authors.forename: Jill
authors.initials: J
authors.lastname: Magee
authors.forename: Christopher
authors.initials: C
authors.lastname: Angel
authors.forename: Alexander
authors.initials: A
authors.lastname: Dobrovic
authors.forename: Grant A
authors.initials: GA
authors.lastname: McArthur
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine; D002648:Child; D005260:Female; D005787:Gene Frequency; D018698:Glutamic Acid; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D010858:Pigmentation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D013912:Threonine; D014633:Valine
chemical_list: D013912:Threonine; D018698:Glutamic Acid; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D014633:Valine; D000409:Alanine