Loss of heterozygosity (LOH) for markers on chromosome 8q in a human chondrosarcoma cell line and in a tumor that developed in a man with Hereditary Multiple Exostoses (HME)
- Univ. of Washington, Seattle, WA (United States); and others
HME is an autosomal dominant disorder in which multiple benign cartilage-capped lesions develop on otherwise histologically normal bones. The majority of chondrosarcomas are sporadic, but the presence of HME greatly increases the risk to develop this tumor. Sarcoma may also arise in sporadically-occurring exostoses. The study of inherited disorders that predispose to malignant diseases has led to discoveries regarding molecular changes involved in carcinogenesis in general. In an analogous manner, somatic mutations in HME genes may be responsible for sporadic exostoses and/or chondrosarcomas. HME is genetically heterogeneous; EXT genes have been assigned to 8q24, the pericentromeric region of 11 and 19p11-p13. We compared chondrosarcoma cell DNA to DNA from white blood cells for LOH at polymorphic loci in these 3 regions. LOH for 4 of 5 markers in 8q24 was detected in a chondrosarcoma that arose in a man with HME. Heterozygosity was retained for markers and chromosomes 11 and 19. We then evaluated cultured cells from 10 sporadic chondrosarcomas. LOH for multiple markers in 8q24 was detected in a cell line, Ch-1, established from an aggressive tumor, but not in 9 other tumors. Of the 9 tumors studied, only the Ch-1 line exhibited LOH for chromosome 11 markers. LOH for a 19p marker was not detected in any of 6 tumors examined, including Ch-1. The karyotype of Ch-1 contains many structurally rearranged chromosomes. The two chromosome 11s appear normal but both chromosome 8 homologues have been replaced by der(8)t(5;8)(q22;q21.2). LOH at 8q24 was also detected in the uncultured tumor. These results suggest that genes responsible for HME may have tumor suppressor functions whose loss may be related to the development of a subset of chondrosarcomas.
- OSTI ID:
- 133563
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0291
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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ANIMAL CELLS
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HEREDITARY DISEASES
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