Genetic models of osteochondroma onset and neoplastic progression: Evidence for mechanisms alternative to EXT genes inactivation

M. Zuntini, E. Pedrini, A. Parra, F. Sgariglia, F. V. Gentile, M. Pandolfi, M. Alberghini, L. Sangiorgi

Research output: Contribution to journalArticlepeer-review


Osteochondroma, the most common benign bone tumor, may occur as a sporadic lesion or as multiple neoplasms in the context of multiple osteochondromas syndrome. The most severe complication is malignant transformation into peripheral secondary chondrosarcoma. Although both benign conditions have been linked to defects in EXT1 or EXT2 genes, contradictory reports are present in the literature regarding the requirement of their biallelic inactivation for osteochondroma development. A major limitation of these studies is represented by the small number of samples available for the screening. Taking advantage of a large series of tissues, our aim was to contribute to the definition of a genetic model for osteochondromas onset and transformation. EXT genes point mutations and big deletions were analyzed in 64 tissue samples. A double hit was found in 5 out of 35 hereditary cases, 6 out of 16 chondrosarcomas and 2 recurrences; none of the 11 sporadic osteochondromas showed two somatic mutations. Our results clearly indicate that, in most cases, biallelic inactivation of EXT genes does not account for osteochondromas formation; this mechanism should be regarded as a common feature for hereditary osteochondromas transformation and as an event that occurs later in tumor progression of solitary cases. These findings suggest that mechanisms alternative to EXT genetic alteration likely have a role in osteochondromas pathogenesis.

Original languageEnglish
Pages (from-to)3827-3834
Number of pages8
Issue number26
Publication statusPublished - Jul 1 2010


  • chondrosarcoma
  • EXT genes
  • multiple osteochondroma
  • mutation screening
  • solitary osteochondroma
  • tumor suppressor

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology


Dive into the research topics of 'Genetic models of osteochondroma onset and neoplastic progression: Evidence for mechanisms alternative to EXT genes inactivation'. Together they form a unique fingerprint.

Cite this