Concomitant loss of chromosome 3 and whole arm losses and gains of chromosome 1, 6, or 8 in metastasizing primary uveal melanoma

PURPOSE. To elucidate the genetic differences between metastasizing and non metastasizing primary tumors, uveal melanoma samples were screened for DNA copy number alterations by comparative genomic hybridization (CGH). METHODS. DNA copy number changes were studied on 14 primary uveal melanomas that had not metastasized, 15 primary uveal melanomas that had metastasize d, and on 6 metastases that were available from 6 primary uveal melanomas. CGH is based on quantitation of the fluorescence intensity of differentiall y labeled DNAs. Tumor DNA labeled with FITC dCTP and dUTP and normal DNA la beled with Texas red dCTP and dUTP were hybridized to normal metaphase chro mosomes. The hybridizations were analyzed using an Olympus fluorescence mic roscope and the ISIS digital image analysis system to identify gain or loss of genetic material. RESULTS. Primary uveal melanomas that had metastasized and metastases had s ignificantly more changes than primary uveal melanomas that had not metasta sized. Comparison between primary nonmetastasizing tumors, metastasizing tu mors, and metastases showed that the most common DNA copy number changes we re -3 (21%, 73%, 67%, respectively), -6q (7%, 40%, 83%), -1p (0, 33%, 33%), -13q (14%, 13%, 50%), -8p (14%, 27%, 0), -18 (7%, 13%, 33%), +8q (14%, 53% , 100%), +6p (29%. 20%, 17%), +1q (0, 7%, 33%), and +16p (0, 7%, 33%). CONCLUSIONS. LOSS Of chromosome 3, loss of 6q, and gain of 8q were signific antly associated with poor overall survival. In addition, losses of Ip were only found in primary uveal melanomas that had metastasized and in metasta ses, which suggests that this region may harbor a tumor suppressor gene imp ortant in the tumor progression. Finally, Loss of chromosome 3 may be assoc iated with isochromosome formation of 1q, Gp, 8q, 16p, 20q, and 22q.