VHL gene alterations in Italian patients with isolated renal cell carcinomas

Lucia Anna Muscarella, Leonardo D'Agruma, Annamaria la Torre, Maddalena Gigante, Michelina Coco, Paola Parrella, Michele Battaglia, Giuseppe Carrieri, Massimo Carella, Leopoldo Zelante, Vito Michele Fazio, Loreto Gesualdo, Elena Ranieri

Research output: Contribution to journalArticlepeer-review


Clear cell renal cell carcinoma (ccRCC) is the most common malignant neoplasm of the kidney and belongs to the few human tumors known to develop from mutations of the VHL tumor suppressor gene. VHL germline mutations are associated with hereditary ccRCCs in VHL disease. However, somatic VHL gene defects may also occur in sporadic ccRCCs. In this study, we analyzed the frequency and the spectrum of VHL gene alterations in 35 Italian patients with sporadic renal cell carcinoma (RCC). Tumor-specific intragenic VHL pathogenic mutations were detected in 38% (11/29) of the ccRCC patients and 33% (2/6) of the patients with other types of RCC. One novel 18-bp in-tandem duplication and 4 previously unreported nucleotide changes in the VHL gene were described. Microsatellite analysis showed loss of heterozygosity for at least 1 informative marker in 43% (9/21) of the ccRCCs and 50% (3/6) of the non-ccRCCs; 5 of the 13 tumors (38%) harboring VHL gene alterations also had loss of heterozygosity for at least 1 microsatellite marker. Our results confirm that somatic inactivation of the VHL gene may play a pivotal role in the tumorigenesis of sporadic ccRCCs in Italian patients and suggests that mutation analysis of the VHL gene may be helpful for discriminating sporadic, VHL-gene-related ccRCCs from those related to VHL disease.

Original languageEnglish
Pages (from-to)208-215
Number of pages8
JournalInternational Journal of Biological Markers
Issue number2
Publication statusPublished - Apr 2013


  • Mutations
  • RCCs
  • Sporadic
  • VHL

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cancer Research
  • Oncology
  • Pathology and Forensic Medicine


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