a metastasis modifier locus on human chromosome 8p in uveal melanoma identified by integrative genomic analysis purpose to identify genes that modify metastatic risk in uveal melanoma a type of cancer that is valuable for studying metastasis because of its remarkably consistent metastatic pattern and wellcharacterized gene expression signature associated with metastasisexperimental design we analyzed 53 primary uveal melanomas by gene expression profiling arraybased comparative genomic hybridization arraybased global dna methylation profiling and single nucleotide polymorphismbased detection of loss of heterozygosity to identify modifiers of metastatic risk a candidate gene leucine zipper tumor suppressor1 lzts1 was examined for its effect on proliferation migration and motility in cultured uveal melanoma cellsresults in metastasizing primary uveal melanomas deletion of chromosome 8p1222 and dna hypermethylation of the corresponding region of the retained hemizygous 8p allele were associated with more rapid metastasis among the 11 genes located within the deleted region lzts1 was most strongly linked to rapid metastasis lzts1 was silenced in rapidly metastasizing and metastatic uveal melanomas but not in slowly metastasizing and nonmetastasizing uveal melanomas forced expression of lzts1 in metastasizing uveal melanoma cells inhibited their motility and invasion whereas depletion of lzts1 increased their motilityconclusions we have described a metastatic modifier locus on chromosome 8p and identified lzts1 as a potential metastasis suppressor within this region this study shows the utility of integrative genomic methods for identifying modifiers of metastatic risk in human cancers and may suggest new therapeutic targets in metastasizing tumor cells