strated by loss of the remaining wild-type allele in hereditary osteochondromas [4]. Whether complete inactivation occurs in sporadic cases remains to be investigated. One or more additional genetic alterations may then be required for a peripheral chondrosarcoma to arise within its benign precursor. The process of malignant transformation is genetically represented by chromosomal instability with severe aneuploidy and a high LOH incidence in peripheral chondrosarcoma [8,9].
Finally, in their discussion of the physiological function of the EXT gene family, the authors omit the important ยฎnding that an EXT1 homologue in Drosophila (tout-velu) was demonstrated to be required for diffusion of the morphogen Hedgehog [10]. Remarkably, in humans, Indian Hedgehog is normally expressed in the growth zone and pre-hypertrophic chondrocytes of cartilage [11]. Furthermore, not only the EXT1 but also the EXT2 gene products were shown to be glycosyltransferases required for the biosynthesis of heparan sulphate [12,13]. The role of the resulting altered heparan sulphate expression on the cell surface and the abnormal diffusion of Hedgehog within chondrocytes of the growth plate caused by EXT mutations will be an interesting ยฎeld of study in the future, further revealing the pathogenesis of osteochondroma.