title: Recurrent GNAQ mutations in anastomosing hemangiomas.
abstract: Anastomosing hemangiomas are recently described benign vascular lesions that occur chiefly in the genitourinary tract and paravertebral soft tissues. Owing to their rarity and unusual cytoarchitectural features, anastomosing hemangiomas are frequently confused with low-grade angiosarcomas. The specific genetic alterations underlying these lesions are currently unknown. We performed capture-based next-generation DNA sequencing analysis on 13 anastomosing hemangiomas and identified frequent somatic mutations in the heterotrimeric G-protein alpha-subunit, GNAQ. Nine of 13 cases (69%) harbored a somatic mutation at GNAQ codon 209, a known hotspot that is commonly mutated in uveal melanoma and blue nevi, as well as various congenital vascular proliferations. No other pathogenic or likely pathogenic mutations were identified in these genetically simple lesions. The finding of a recurrent driver mutation in the G-protein signal transduction pathway provides strong evidence that anastomosing hemangiomas are indeed clonal vascular neoplasms.
authors.affiliation: Department of Pathology, University of California, San Francisco, CA, USA.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Bean
authors.affiliation: Department of Pathology, University of California, San Francisco, CA, USA.
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Joseph
authors.affiliation: Department of Pathology, University of California, San Francisco, CA, USA.
authors.forename: Ryan M
authors.identifier: 0000-0001-6229-7928
authors.initials: RM
authors.lastname: Gill
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Folpe
authors.affiliation: Department of Pathology, University of California, San Francisco, CA, USA.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Horvai
authors.affiliation: Department of Pathology, University of California, San Francisco, CA, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Umetsu
mesh_terms: D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics*; D006391:Hemangioma / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: C554061:GNAQ protein, human; D043802:GTP-Binding Protein alpha Subunits, Gq-G11