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Localization of a Novel Tumor Suppressor Locus on Human Chromosome 3q Important in Osteosarcoma Tumorigenesis¹

Departments of Molecular Genetics [R. P. K., M. F. H.], Tumor Biology [E. C. M.], and Experimental Pediatrics [L. C. S.], University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, and Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284 [S. L. N.]

Mitotic recombination or nondysjunction are common mechanisms for tumor-specific loss of constitutional heterozygosity (LOH) and tumor suppressor allelic inactivation and can be useful in localizing new putative tumor suppressor genes. In osteosarcoma, the highest frequencies of LOH have been reported for chromosomes 3q, 13q, 17p, and 18q. The high incidence of LOH on chromosome 3q suggests the presence of a novel tumor suppressor gene. To localize this putative tumor suppressor gene, we have used polymorphic markers on chromosome 3q to define the minimal region in which mitotic recombination or deletion results in LOH, which should contain the tumor suppressor gene. This putative tumor suppressor has been localized to a region between 3q26.2-3q26.3 of less than 1 cM between the polymorphic loci D3S1212 and D3S1246.

¹ This work was supported by Grants CA53318 and CA60122 (to M. F. H.), CA34936 (to L. C. S.), CA56626 and H600470 (to S. L. N.) from the NIH and by Training Grant CA09299 from the National Cancer Institute (to R. P. K.).

² To whom requests for reprints should be addressed, at Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, PA 19140. Phone: (215) 707-4300; Fax: (215) 707-1454; E-mail: mfh@sgil.fels.temple.edu.

Received 6/27/96. Accepted 11/ 1/96.

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