title: Activating mutations in the RAS/mitogen-activated protein kinase signaling pathway in sporadic trichoblastoma and syringocystadenoma papilliferum.
abstract: Trichoblastoma (TB) and syringocystadenoma papilliferum (SCAP) are both rare adnexal skin lesions occurring either sporadically or as secondary neoplasms in sebaceous nevi. TB and SCAP associated with sebaceous nevi have been shown to carry the same HRAS mutation as the underlying nevus. However, the genetic background of sporadic TB and SCAP has remained unknown. Therefore, we screened 18 sporadic TBs and 23 sporadic syringocystadenoma papillifera from 41 patients for the presence of activating mutations in RAS genes and other oncogenes. Using a RAS SNaPshot assay, HRAS mutations were detected in 2 (11%) of 18 sporadic TB and 6 (26%) of 23 sporadic syringocystadenoma papillifera. A KRAS mutation was identified in 1 sporadic SCAP. High-throughput oncogene mutation profiling furthermore identified BRAF V600E mutations in sporadic syringocystadenoma papillifera, which could be validated in 12 (52%) of 23 lesions using a BRAF SNaPshot assay. BRAF and RAS mutations were mutually exclusive in sporadic syringocystadenoma papillifera. No BRAF mutation could be detected in 3 syringocystadenoma papillifera secondarily arisen from a sebaceous nevus as well as in sporadic TB. In 14 lesions carrying an oncogenic mutation, nonlesional control tissue from the epidermal margin revealed a wild-type sequence, thus proving the somatic character of the mutation. Our results indicate that activation of the RAS-mitogen-activated protein kinase pathway by BRAF and RAS mutations contributes significantly to the tumorigenesis of sporadic SCAP and, less frequently, of sporadic TB.
authors.affiliation: Department of Dermatology, University of Regensburg, 93053 Regensburg, Germany.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Shen
authors.affiliation: Department of Dermatology, University of Regensburg, 93053 Regensburg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Peterhof
authors.affiliation: Dermatohistological Laboratory Prof. Kind, 63065 Offenbach, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kind
authors.affiliation: Dermatopathology Friedrichshafen, 88048 Friedrichshafen, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Rütten
authors.affiliation: Department of Dermatology and Venerology, Medical University Innsbruck, 6020 Innsbruck, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zelger
authors.affiliation: Department of Dermatology, University of Regensburg, 93053 Regensburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Landthaler
authors.affiliation: Department of Dermatology, University of Regensburg, 93053 Regensburg, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Berneburg
authors.affiliation: Department of Dermatology, University of Regensburg, 93053 Regensburg, Germany; Dermatohistological Laboratory, Sonnenstr. 7, 80331 Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hafner
authors.affiliation: Department of Dermatology, University of Regensburg, 93053 Regensburg, Germany. Electronic address: leopold.groesser@ukr.de.
authors.forename: Leopold
authors.initials: L
authors.lastname: Groesser
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009506:Nevus / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D048493:Proto-Oncogene Proteins B-raf; D020928:Mitogen-Activated Protein Kinases
keywords: BRAF; HRAS; KRAS; Syringocystadenoma papilliferum; Trichoblastoma