title: Molecular dissection of the VHL gene in solitary capillary hemangioblastoma of the central nervous system.
abstract: Capillary hemangioblastomas (HGBs) of the CNS occur either sporadically or as part of the von Hippel-Lindau (VHL) syndrome. Molecular characterizations of the VHL gene in sporadic HGBs at the somatic level have been limited to date. We investigated the VHL gene in 57 patients most of whom (55 [96%] of 57) had a solitary CNS HGB at the time of surgery. Tissues from 23 HGBs of these patients (2 VHL related and 21 unrelated) were also investigated at genetic and epigenetic levels. Two of the 51 patients with apparently sporadic HGBs and no additional evidence of VHL (∼4%) were found to have a germline VHL gene mutation; both of these patients subsequently developed evidence of VHL syndrome. Somatic VHL gene mutations were found in 11 (52%) of the 21 non-VHL-related cases. A germline mutation was identified in 5 (84%) of 6 VHL-associated HGBs; double gene inactivation was observed in tumor tissue from VHL syndrome patients. Seven different previously unreported VHL gene alterations (6 somatic and 1 germline) were identified; double hits were identified in 7 (12%) of 57 cases. Our findings confirm the usefulness of VHL gene analysis at the germline level in patients who present with apparently solitary HGB. Moreover, the genetic and epigenetic VHL gene investigations performed support a key role for functional alterations of the VHL gene in sporadic neuraxial HGB.
authors: From the Laboratory of Oncology (LAM, AlT, AF, PP, MC, VMF), and Departmentof Neurosurgery (DC, VDA), IRCCS "Casa Sollievo della Sofferenza," San Giovanni Rotondo; IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture (MB);Medical Genetics Service, Evolutive Age Department (LZ, LDA), and Research Unit of Diabetes and Endocrine Diseases (GF), IRCCS "Casa Sollievo della Sofferenza," San Giovanni Rotondo; Department of Neurosurgery, "San Filippo Neri" Hospital, Rome (AT); and Laboratory of Molecular Medicine and Biotechnology, Interdisciplinary Center for Biomedical Research, University Campus BioMedico, Rome (VMF), Italy.
authors: Lucia Anna
authors: LA
authors: Muscarella
authors: Annamaria
authors: A
authors: la Torre
authors: Augusta
authors: A
authors: Faienza
authors: Demenico
authors: D
authors: Catapano
authors: Michele
authors: M
authors: Bisceglia
authors: Vincenzo
authors: V
authors: D'Angelo
authors: Paola
authors: P
authors: Parrella
authors: Michelina
authors: M
authors: Coco
authors: Grazia
authors: G
authors: Fini
authors: Angelo
authors: A
authors: Tancredi
authors: Leopoldo
authors: L
authors: Zelante
authors: Vito Michele
authors: VM
authors: Fazio
authors: Leonardo
authors: L
authors: D'Agruma
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D002196:Capillaries / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D018095:Germ-Line Mutation / Q000235:genetics; D018325:Hemangioblastoma / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*; D055815:Young Adult
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human