Molecular and functional evidence for the presence of a tumor-suppressor gene on human chromosome 11

Abstract

Cytogenetic analysis of human intraspecific HeLa X fibroblast hybrids has implicated the loss of a single copy of chromosome 11 and 14 in the reexpression of tumorigenicity. Molecular analysis of the paired combination of non tumongenic and tumongemc hybrids using chromosome 11- and 14-specific restnctionfragment length polymorphic (RFLP) probes has identified the loss of a fibroblast chromosome 11 in the tumorigenic hybrid cells. There was no obvious correlation between the loss of normal chromosome 14 and the reexpression of the tumorigenic phenotype. The presence of the tumor-suppressor sequences on normal chromosome 11 was further confirmed by the derivation of non-tumorigenic cells with the introduction of a single copy of fibroblast chromosome 11 into the tumorigenic cells. The precise location of the tumor suppressor sequences was then determined by an extensive RFLP analysis of the HeLa X normal chromosome 11 hybrids using a large numher of chromosome l1-spccific probcs. These results showed a perfect correlation between the presence of the long arm (q-arm) of chromosome 11 and the suppression of the tumongenic phenotype. Also, one of the tumorigenic hybrids had lost q 13-specdic genetic markers while retaining other regions of the chromosome. We conclude therefore that the gene(s) involved in the suppression of the HeLa tumors is localized to the long arm of chromosome t 1, most likely to the q13 region.