Details

Autor(en) / Beteiligte

• Bridge, Julia A.
• Nelson, Mari
• Örndal, Charlotte
• Bhatia, Paramjit
• Neff, James R.

Titel

Clonal karyotypic abnormalities of the hereditary multiple exostoses chromosomal loci 8q24.1 (EXT1) and 11p11‐12 (EXT2) in patients with sporadic and hereditary osteochondromas

Ist Teil von

• Cancer, 1998-05, Vol.82 (9), p.1657-1663

Ort / Verlag

New York: John Wiley & Sons, Inc

Erscheinungsjahr

1998

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• BACKGROUND Osteochondroma most frequently arises sporadically and as a solitary lesion, but also may arise as multiple lesions characterizing the autosomal dominant disorder hereditary multiple exostoses (HME) and the contiguous gene syndromes Langer‐Giedion and DEFECT‐11 syndromes. HME is genetically heterogeneous with association of three loci including 8q24.1 (EXT1), 11p11‐12 (EXT2), and 19p (EXT3). Constitutional chromosomal microdeletions of 8q24.1 and 11p11‐12 are features of the Langer‐Giedion and DEFECT‐11 syndromes, respectively. Cytogenetic studies of osteochondroma are rare. METHODS Cytogenetic analysis was performed on 34 osteochondroma specimens from 22 patients with sporadic lesions and 4 patients with HME utilizing standard methodologies. Fluorescence in situ hybridization with chromosome specific probes was performed on three cases to define structural rearrangements further. RESULTS Clonal abnormalities were detected in ten cases. Notably, deletion 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 hereditary tumor). CONCLUSIONS These findings: 1) confirm previous observations of 8q24.1 karyotypic anomalies in sporadic osteochondroma, 2) reveal the presence of somatic chromosomal anomalies in hereditary osteochondromata, 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 mutation of EXT1 and EXT2, two putative tumor suppressor genes, may be important in the pathogenesis of sporadic as well as hereditary osteochondromata. Cancer 1998;82:1657‐63. © 1998 American Cancer Society. Genetic analysis of 34 osteochondromas from 26 patients with and without hereditary multiple exostoses (HME) revealed loss or rearrangement of two HME‐associated loci: 8q24.1 (EXT1) and 11p11‐12 (EXT2). These findings support the hypothesis that loss or mutation of EXT1 and EXT2, putative tumor suppressor genes, may be important in the pathogenesis of sporadic as well as hereditary osteochondromata and suggest that similar to hereditary lesions, sporadic osteochondromas also are genetically heterogeneic.