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Potential Gastrointestinal Tumor Suppressor Locus at the 3p14.2 FRA3B Site Identified by Homozygous Deletions in Tumor Cell Lines¹

Jefferson Cancer Institute [K. K., R. B., T. D., M. O., M. G. C., H.I., C. M. C., K. H.] and Department of Surgical Pathology [J. P.], Jefferson Medical College, Philadelphia Pennsylvania 19107-6799; Department of Pathology, University of Padova, Padova, Italy [M. R.]; and Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong [D. H.]

A number of DNA fragments, identified by representational difference analysis, 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 localized the probe to 3p14.2, 350 kbp telomeric to the 3p14.2 break of the t(3;8) hereditary renal cell carcinoma chromosome translocation, within or near the 3p14.2 FRA3B, the most common human fragile site. We determined the sizes of the homozygous deletions in a number of cancer cell lines after isolation of a yeast artificial chromosome contig and development of STS markers which fall between D3S1234 and D3S1481, which flank the deletions. Homozygous deletions were observed and sized not only in the cell lines originally reported but also in a number of nasopharyngeal carcinoma cell lines and a gastric carcinoma cell line. About 50% of uncultured stomach and colon carcinomas were then 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 cell lines harbors an important tumor suppressor gene for several tumor types.

¹ This work was supported by USPHS Grant CA51083, and a gift from R. R. M. Carpenter III and Mary K. Carpenter. National Cancer Institute Cancer Center Grant CA56336 supported the Jefferson Cancer Center shared research facilities, which expedited the study.

² To whom requests for reprints should be addressed, at Jefferson Cancer Institute, Bluemle Life Sciences Building, Room 1008, 233 South 10th Street, Jefferson Medical College, Philadelphia PA 19107. Phone (215) 955-4656; Fax (215) 923-4498.

Received 12/21/95. Accepted 1/17/96.

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