OSTEOGENIC SARCOMA: ASSESSMENT OF TUMOR NECROSIS WITH DYNAMIC MR IMAGING AFTER NEOADJUVANT CHEMOTHERAPY - WORK IN PROGRESS

Panicek DM, Dyke JP, Ballon DJ, Koutcher JA, Schwartz LH, Healey JH, Meyers PA, Huvos AG (Memorial Sloan-Kettering Cancer Center, New York, NY 10021).

REFINEMENT OF A COMMONLY DELETED SEGMENT OF CHROMOSOME ARM 18q IN 6-OSTEOSARCOMA

Gibbs, Jr. CP, Wang PW, LeBeau MM (University of Colorado Health Sciences Center, Denver, CO, 80262)

A number of genetic alterations implicated in the pathogenesis of solid tumors such as breast and colon carcinoma have been identified. Similar changes have not been well characterized in sarcomas, particularly osteosarcoma. Recent investigations have localized allele loss to chromosome arms 3q, 13q, 17p, 18q, 6p, 10q, and 15q in greater than 50% of osterosarcoma specimens evaluated. Loss of genetic material is felt to be indicative of potential tumor suppressor genes in that area.

In an attempt to further localize potential suppressor genes in osteosarcoma on chromosome arm 18q, we performed allele loss studies (loss of heterozygosity) on 84 patients tumor DNA. This is a PCR based assay utilizing radiolabeled microsatellite markers distributed over the length of 18q.

Sixty-five percent of the tumors evaluated exhibited loss of genetic material at 18q. Most were missing large areas of the chromosome arm. However, we were able to identify a commonly deleted region of less than one megabase on the distal aspect of 18q bordered by microsatellite markers D18S-848 and D18S-541. The smallest commonly deleted region was defined by four patient samples. In addition, we have constructed a partial YAC and PAC contig across this region to facilitate possible identification of potential tumor suppressor genes. This region is distal to the known tumor suppressor genes, DPC4 and DCC also on chromosome arm 18q.