title: BRAF and RAS Mutations in Sporadic and Secondary Pyogenic Granuloma.
abstract: Pyogenic granuloma (PG) is a common benign vascular skin lesion presenting as a rapidly growing angiomatous papule. The pathogenesis of most sporadic PGs and PGs associated with port wine stains (PWSs) remains elusive. We report that of 10 PGs secondarily arisen on a PWS, 8 showed a BRAF c.1799T>A (p.(Val600Glu)) and 1 a NRAS c.182A>G (p.(Gln61Arg)) mutation. The GNAQ c.548G>A mutation was identified in the PG and in the respective underlying PWS, indicating that PGs originate from cells of the PWS. In contrast to PG, 12 papulonodular lesions, which had developed in the PWSs of seven patients, showed a RAS and BRAF wild-type status. In sporadic PG we identified the BRAF c.1799T>A mutation in 3 of 25, a BRAF c.1391G>A mutation in 1 of 25, and a KRAS c.37G>C mutation in 1 of 25. Mutation-specific immunohistochemical detection of BRAF p.(Val600Glu) confirmed endothelial cells as carriers of the mutation in secondary and sporadic PG. Our study identifies the BRAF c.1799T>A mutation as a major driver mutation in the pathogenesis of, particularly, secondary PG. These data shed light on the hitherto undetermined genetic basis of PG and classify PG as a benign neoplasm.
authors.affiliation: Department of Dermatology, University of Regensburg, Regensburg, Germany. Electronic address: leopold.groesser@ukr.de.
authors.forename: Leopold
authors.initials: L
authors.lastname: Groesser
authors.affiliation: Department of Dermatology, University of Regensburg, Regensburg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Peterhof
authors.affiliation: Institute of Pathology, University of Regensburg, Regensburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Evert
authors.affiliation: Department of Dermatology, University of Regensburg, Regensburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Landthaler
authors.affiliation: Department of Dermatology, University of Regensburg, Regensburg, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Berneburg
authors.affiliation: Dermatohistological Laboratory, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hafner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D002648:Child; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D017789:Granuloma, Pyogenic / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D012871:Skin Diseases / Q000235:genetics* / Q000473:pathology
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf