CLONING OF THE PUTATIVE TUMOR-SUPPRESSOR GENE FOR HEREDITARY MULTIPLEEXOSTOSES (EXT1)

Hereditary multiple exostoses is an autosomal dominant disorder that i s characterized by short stature and multiple, benign bone tumours. In a majority of families, the genetic defect (EXT1) is linked to the La nger-Giedion syndrome chromosomal region in 8q24.1. From this region w e have cloned and characterized a cDNA which spans chromosomal breakpo ints previously identified in two multiple exostoses patients. Further more, the gene harbours frameshift mutations in affected members of tw o EXT1 families. The cDNA has a coding region of 2,238 bp with no appa rent homology to other known gene sequences and thus its function rema ins elusive. However, recent studies in sporadic and exostosis-derived chondrosarcomas suggest that the 8q24.1-encoded EXT1 gene may have tu mour suppressor function.