Analysis of tumor suppressor gene on human chromosome 9 in mouse x human somatic cell hybrids.

Deletions of the short arm of human chromosome 9 (9p) are common in human leukemia and solid tumors. The minimum region of overlap of these deletions, located between the interferon genes and the methylthioadenosine phosphorylase gene, is partially syntenic with a region of mouse chromosome 4 that has tumor suppressor activity. Somatic cell hybrids between tumorigenic, MTAP-deficient, mouse L cells, and MTAP-competent human cells containing either a normal copy of 9p or a 9p with a deletion involving band 9p21 were selected in culture conditions that require MTAP activity for continued growth. Somatic cell hybrids that contained a normal copy of 9p rarely formed tumors in nude mice. Cells from the rare tumors that grew had lost the normal 9p. Hybrid cells that contained a 9p with deletions formed tumors more frequently, and cells from these tumors retained the 9p deletion chromosome. These results provide evidence that a tumor suppressor gene (or genes) is located on human chromosome 9 within the region of deletion.