High-Resolution Array CGH Analysis Identifies Regional Deletions and Amplifications of Chromosome 8 in Uveal Melanoma

Monosomy 3 (M3) and abnormalities of chromosome 8 associate with poor prognosis in uveal melanomas (UM). Although M3 has been the subject of more in-depth studies, none have intensively focused on chromosome 8. To elucidate the potential role of chromosome 8 abnormalities, array comparative genomic hybridization (aCGH) was performed on primary UM.

A specifically-designed custom high-resolution array was developed focusing on changes most implicated in UM. Probes for chromosome 8 had a mean spacing of 2.3 kb while chromosomes infrequently affected had a mean spacing of 36.6 kb. A series of 75 UM, including one formalin-fixed paraffin sample were analyzed, and where possible control DNA extracted from the patient's own peripheral blood was used.

The most common copy number abnormalities were chromosome 8 (75%) and M3 (51%), with M3 and gain of the long arm of chromosome 8 (8q+) associated in 41% of cases. Also identified were partial deletions of chromosome 3 (3%) and regional 8q+ (23%), and the intensive coverage of chromosome 8 revealed small focal deletions and amplifications affecting both arms. The most significant predictor of prognosis was M3/8q+ having a hazard ratio of 10.1 (P < 0.0001).

Neither 8p deletion nor focal changes affecting chromosome 8 were linked to outcome. The most significant indicator was M3/8q, and multiple 8q+ associated with shorter survival. Studying UM with this technology provides a powerful robust tool for predicting prognosis while considering other genetic changes, allowing the future incorporation of such data as it becomes clinically significant.