The introduction of normal chromosomes into tumor cells by microcell fusion-mediated transfer is a powerful technique to identify putative tumor suppressor genes. We have used this approach to independently transfer human chromosomes 3 and 12 into a human prostate cancer cell line, DU 145. We showed that while the extra copy of chromosome 3 had no effect on the in vivo tumorigenicity of these cells, microcell hybrids containing an introduced portion of chromosome 12 (12pter-12q13) exhibited complete suppression of tumorigenicity in athymic nude mice. The presence of a dual selectable marker facilitated the selection for cells having segregated del(12)(q13). Loss of this fragment in three different clones led to reexpression of the malignant phenotype. These results demonstrate that one or more genes on human chromosome 12 function as tumor suppressors of prostate carcinogenesis.

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This work was supported by a grant from the Cancer Research Society, Montréal, Québec, Canada. N. G. B. and M. D. S. are recipients of Ontario Graduate Scholarships.

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