Functional evidence of novel tumor suppressor genes for cutaneous malignant melanoma

Losses of heterozygosity involving chromosomes 9 and 10 are frequent events in the development and progression of cutaneous malignant melanoma, To inv estigate whether specifically deleted chromosomal regions encode tumor supp ressor genes (TSGs), we introduced normal chromosome 10 into the tumorigeni c human metastatic melanoma cell line UACC-903 by microcell fusion. In addi tion, two chromosome 9 derivatives that were microdeleted in the region of the p16(INK4A)/p15(INK4B) locus were transferred to determine whether an ad ditional melanoma TSG or TSGs reside on chromosome 9p, as indicated by prev ious melanoma allele loss studies. In comparison to parental cells, microce ll hybrids generated with chromosomes 9 (microdeleted) and 10 displayed red uced anchorage-independent growth in soft agar and markedly reduced tumorig enicity in athymic (nu/nu) mice. These data define a TSG or TSGs that funct ion independently of p15/p16 on chromosome 9 and provide evidence for a TSG (or TSGs) on chromosome 10 that may be important in melanoma development.