POTENTIAL GASTROINTESTINAL TUMOR-SUPPRESSOR LOCUS AT THE 3P14.2 FRA3BSITE IDENTIFIED BY HOMOZYGOUS DELETIONS IN TUMOR-CELL LINES

A number of DNA fragments, identified by representational difference a nalysis, which were homozygously deleted in various cancer cell lines were previously mapped to human chromosomal arms. One of these, BE758- 6, which was homozygously deleted in a number of colon carcinoma cell lines, had been mapped to chromosome region 3p. We have further locali zed the probe to 3p14.2, similar to 350 kbp telomeric to the 3p14.2 br eak of the t(3;8) hereditary renal cell carcinoma chromosome transloca tion, within or near the 3p14.2 FRA3B, the most common human fragile s ite. We determined the sizes of the homozygous deletions in a number o f cancer cell lines after isolation of a yeast artificial chromosome c ontig and development of STS markers which fall between D3S1234 and D3 S1481, which flank the deletions. Homozygous deletions were observed a nd sized not only in the cell lines originally reported hut also in a number of nasopharyngeal carcinoma cell lines and a gastric carcinoma cell line. About 50% of uncultured stomach and colon carcinomas were t hen shown to lose heterozygosity for alleles in the same region, with a common region of loss between the D3S1234 and D3S1481 markers. Thus, it is likely that the homozygous deletion observed in these cancer ce ll lines harbors an important tumor suppressor gene for several tumor types.