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LOH18CR1; Loss of heterozygosity, 18, chromosomal region 1

Location: 18q21-q22
Alias: OSTS

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Paget disease is a common metabolic bone disease characterized by rapid bone remodeling and abnormal bone formation. It occurs mostly in people aged over 40 yrs. Approximately 1% of Paget patients develop osteosarcoma, which represents an increase in risk that is several thousandfold over that of the general population. Evidence for a novel osteosarcoma tumor-suppressor gene in the chromosome 18 region genetically linked with Paget disease of bone. Nellissery and collegues (1998) Recent evidence suggests that predisposition to Paget disease may have a genetic component. Genetic linkage analysis of families with multigenerational Paget disease shows linkage to a region of chromosome 18q near the polymorphic locus D18S42. Osteosarcoma in Paget patients is the underlying basis for a significant fraction of osteosarcomas occurring after age 60 years. Our analysis of tumor-specific loss of constitutional heterozygosity (LOH) in 96 sporadic osteosarcomas has identified a putative tumor-suppressor locus that maps to chromosome 18q. We have localized this tumor-suppressor locus between D18S60 and D18S42, a region tightly linked to familial Paget disease. Analysis of osteosarcomas from patients with Paget disease revealed that these tumors also undergo LOH in this region. These findings suggest that the association between Paget disease and osteosarcoma is the result of a single gene or two tightly linked genes on chromosome 18.

Nellissery MJ. et al. Evidence for a novel osteosarcoma tumor-suppressor gene in the chromosome 18 region genetically linked with Paget disease of bone. Am J Hum Genet 1998; 63:817-24    Related articles (PubMed)

Hansen MF, et al. Common mechanisms of osteosarcoma and Paget's disease. [Review] J Bone Miner Res 1999; 14 Suppl 2:39-44    Related articles (PubMed)

Medline Search: osteosarcoma AND (LOH18CR1 OR OSTS) (PubMed)   Limit search to: [Last Year]  Limit search to: [Last 2 Years]   Limit search to: [Reviews]

Related Resources
Osteosarcoma Genetics
Osteosarcoma : Clinical and Epidemiological Information

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