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 hu man leukemia and solid tumors. The minimum region of overlap of these deletions, located between the interferon genes and the methylthioaden osine phospholylase 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-competen t human cells containing either a normal copy of 9p or a 9p with a del etion involving band 9p21 were selected in culture conditions that req uire MTAP activity for continued growth. Somatic cell hybrids that con tained a normal copy of 9p rarely formed tumors in nude mice. Cells fr om the rare tumors that gr ew had lost the normal 9p. Hybrid cells tha t contained a 9p with deletions formed tumors more frequently, and cel ls from these tumors retained the 9p deletion chromosome. These result s provide evidence that a tumor suppressor gene (or genes) is located on human chromosome 9 within the region of deletion.