Hereditary multiple exostosis and chondrosarcoma: Linkage to chromosome 11 and loss of heterozygosity EXT-linked markers on chromosomes 11 and 8
- Univ. of Texas Medical School, Houston (United States)
- Univ. of Texas M. D. Anderson Cancer Center, Houston (United States)
- Univ. of Houston, TX (United States)
- Univ. of Virginia, Charlottesville (United States)
Hereditary multiple exostosis (EXT) is an autosomal dominant disorder characterized by bony exostoses at the ends of the long bones. Linkage studies have recently suggested that there are three chromosomal locations for EXT genes, 8q24.1 (EXT1), the pericentric region of 11 (EXT2), and 19p (EXT3). As part of a larger study to determine the frequencies of the three EXT types in the United States, we have ascertained a large multigenerational family with EXT and one family member with a chondrosarcoma. This family demonstrated linkage of the disease to chromosome 11 markers. The constitutional and tumor DNAs from the affected family member were compared using shortandem-repeat markers from chromosomes 8, 11, and 19. Loss of heterozygosity (LOH) in the tumor was observed from chromosome 8 and 11 markers, but chromosome 19 markers were intact. An apparent deletion of the marker D11S903 was observed in constitutional DNA from all affected individuals and in the tumor sample. These results indicate that the EXT2 gene maps to the region containing marker D11S903, which is flanked by markers D11S1355 and D11S1361. Additional constitutional and chondrosarcoma DNA pairs from six unrelated individuals, two of who had EXT, were similarly analyzed. One tumor from an individual with EXT demonstrated LOH for chromosome 8 markers, and a person with a sporadic chondrosarcoma was found to have tumor-specific LOH and a homozygous deletion of chromosome 11 markers. These findings suggest that EXT genes may be tumor-suppressor genes and that the initiation of tumor development may follow a multistep model. 23 refs., 3 figs., 2 tabs.
- OSTI ID:
- 75453
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 5 Vol. 56; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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