Detection of c-myc amplification in uveal melanoma by fluorescent in situ hybridization

PURPOSE. Genetic abnormalities of chromosomal arm 8q have been reported by many studies in uveal melanoma. To better understand the role of 8q abnorma lities in uveal melanoma development, copy number anomalies of the c-myc on cogene (located on 8q24.1) have been investigated. METHODS. Forty-three uveal melanomas were analyzed by fluorescent in situ h ybridization (FISH) with probes for c-myc and the chromosome 8 centromere. Results of the FISH analysis were compared with genetic changes previously detected by microsatellite analysis on chromosomes S and Gp. RESULTS. Thirty uveal melanomas (70%) had extra copies of c-myc, 2 tumors ( 5%) had loss of c-myc, and II tumors (25%) had no abnormalities in c-myc co py number. Of those with extra copies of c-myc, 13 tumors (43%) had amplifi cation of the c-myc gene, 14 tumors (47%) had an intermediate relative incr ease in the c-myc copy number, and 3 tumors (10%) had a simple gain of chro mosome 8. An association between larger tumor size and c-myc amplification was found (P < 0.01). Although extra copies of c-myc were seen in tumors wi th retention of chromosome 3, remarkably only tumors with monosomy 3 showed amplification of c-myc (P = 0.03). CONCLUSIONS. The specific amplification of the c-myc oncogene detected in a t least 30% of primary uveal melanomas cannot be explained by the simple 8q abnormalities observed in cytogenetic studies. The striking association be tween c-myc amplification and monosomy 3 suggests a unique pathway of genet ic progression in a subset of uveal melanomas.