The chromosome 10 monosomy common in human melanomas results from the lossof two separate tumor suppressor loci

Alteration of chromosome 10 is common in human melanomas and usually entail s the loss of an entire chromosome homologue. Although the reasons for mono somy in cancer has remained obscure, one possibility is that multiple tumor suppressor genes residing on this chromosome must be lost in unison during tumor progression, and this is easier to accomplish by chromosome segregat ion rather than by multiple mutational and/or deletion events. The localiza tion and identification of these genes has been hampered by the monosomy it self, which has resulted in a paucity of small defining deletions in tumors . Here, we have addressed the issue of monosomy in tumor development by usi ng functional complementation mapping to localize and demonstrate the exist ence of different melanoma suppressor genes on chromosome 10 and assigned e ach locus a distinct tumorigenic phenotype, We report that a locus on 10q d istal to 10q23.1, likely involving the PTEN tumor suppressor, causes a seve re reduction in the kinetics of melanoma tumor formation in animals. In con trast, a previously unrecognized region at 10p15.3 has a distinct, but less er, effect on in vivo melanoma growth. Thus, the loss of both of these regi ons, which is accomplished by tumor-associated monosomy, provides a signifi cant growth advantage over the individual loss of either region, thereby ex plaining the monosomy observed in sporadic melanomas.