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

• Published in: Investigative ophthalmology & visual science Vol. 56; no. 6; p. 3460
• Main Authors: Hammond, David W., Al-Shammari, Nawal S. D., Danson, Sarah, Jacques, Rhona, Rennie, Ian G., Sisley, Karen
• Format: Journal Article
• Language: English
• Published: United States 01.06.2015
• Subjects: Adult; Aged; Aged, 80 and over; Chromosomes, Human, Pair 8 - genetics; Comparative Genomic Hybridization - methods; DNA Copy Number Variations; Female; Gene Amplification; Genetic Predisposition to Disease - genetics; Humans; Male; Melanoma - genetics; Microarray Analysis - methods; Middle Aged; Monosomy - genetics; Regression Analysis; Sequence Deletion; Survival Analysis; Uveal Neoplasms - genetics; Young Adult
• ISSN: 1552-5783; 1552-5783
• DOI: 10.1167/iovs.14-16215

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.