CLONAL KARYOTYPIC ABNORMALITIES OF THE HEREDITARY MULTIPLE EXOSTOSES CHROMOSOMAL LOCI 8Q24.1 (EXT1) AND 11P11-12 (EXT2) IN PATIENTS WITH SPORADIC AND HEREDITARY OSTEOCHONDROMAS

BACKGROUND. Osteochondroma most frequently arises sporadically and as a solitary lesion, but also may arise as multiple lesions characterizi ng the autosomal dominant disorder hereditary multiple exostoses (HME) and the contiguous gene syndromes Langer-Giedion and DEFECT-11 syndro mes. HME is genetically heterogeneous with association of three loci i ncluding 8q24.1 (EXT1), 11p11-12 (EXT2), and 19p (EXT3). Constitutiona l chromosomal microdeletions of 8q24.1 and 11p11-12 are features of th e Langer-Giedion and DEFECT-11 syndromes, respectively. Cytogenetic st udies of osteochondroma are rare. METHODS. Cytogenetic analysis was pe rformed on 34 osteochondroma specimens from 22 patients with sporadic lesions and 4 patients with HME utilizing standard methodologies. Fluo rescence in situ hybridization with chromosome specific probes was per formed on three cases to define structural rearrangements further.RESU LTS. Clonal abnormalities were detected in ten cases. Notably, deletio n of 11p11-13 was observed in one case (a sporadic tumor) and loss or rearrangement of 8q22-24.1 in eight cases (seven sporadic and one here ditary tumor). CONCLUSIONS. These findings: 1) confirm previous observ ations of 8q24.1 karyotypic anomalies in sporadic osteochondroma, 2) r eveal the presence of somatic chromosomal anomalies in hereditary oste ochondromata, 3) suggest that similar to hereditary lesions, sporadic osteochondromas also are genetically heterogeneic (involvement of both 8q24.1 and 11p11-12), and 4) support the hypothesis that loss or muta tion of EXT1 and EXT2, two putative tumor suppressor genes, may be imp ortant in the pathogenesis of sporadic as well as hereditary osteochon dromata. (C) 1998 American Cancer Society.