Molecular dissection of the VHL gene in solitary capillary hemangioblastoma of the central nervous system

Lucia Anna Muscarella, Annamaria La Torre, Augusta Faienza, Demenico Catapano, Michele Bisceglia, Vincenzo D'Angelo, Paola Parrella, Michelina Coco, Grazia Fini, Angelo Tancredi, Leopoldo Zelante, Vito Michele Fazio, Leonardo D'Agruma

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)50-58
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Issue number1
Publication statusPublished - Jan 2014


  • Genetic analysis
  • Hemangioblastoma
  • Mutation
  • von Hippel-Lindau disease.

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience


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