Frequent loss of heterozygosity for markers on chromosome arm 10q in chondrosarcomas.
Many tumors exhibit loss of heterozygosity (LOH) for polymorphic markers in regions of the genome that contain genes whose normal function can suppress tumor growth. Mapping of regions of LOH can help identify putative tumor suppressor loci that play a role in the pathogenesis of a disease. We evaluated 18 chondrosarcomas for LOH at 17 short tandem-repeat polymorphism loci on chromosome 10. Sixty-seven percent of the tumors (12/18) showed LOH for at least one marker and in most of these tumors the region of loss spanned all or large portions of the chromosome. By determining the smallest segment consistently involved, we identified a 7-12 cM critical region for LOH in the proximal long arm. This genomic region contains the RET oncogene, which has been implicated in the pathogenesis of multiple endocrine neoplasia types 2A and 2B, Hirschsprung disease, and medullary and papillary thyroid carcinomas. LOH on chromosome arm 10q was found in early-stage chondrosarcomas and did not correlate with grade or prognosis. Inactivation or alteration of a gene located at this site may be an early event in the development of these tumors.
Raskind
W H
WH
Department of Medicine, University of Washington, Seattle 98195, USA. wendyrun@u.washington.edu
Conrad
E U
EU
Matsushita
M
M
D001859:Bone Neoplasms / Q000235:genetics*; D002813:Chondrosarcoma / Q000235:genetics*; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D002880:Chromosomes, Human, Pair 11; D002888:Chromosomes, Human, Pair 19; D002898:Chromosomes, Human, Pair 8; D017353:Gene Deletion; D005819:Genetic Markers; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D012150:Polymorphism, Restriction Fragment Length
D005819:Genetic Markers