title: Frequency, molecular pathology and potential clinical significance of partial chromosome 3 aberrations in uveal melanoma.
abstract: The clinical significance of partial chromosome 3 alteration in uveal melanoma is still not clear. Also, the reported frequencies vary considerably in the published literature from 0 to 48%. The aims of the following study were to identify the frequency, molecular pathology and potential clinical significance of partial chromosome 3 alteration in uveal melanoma. We studied 47 uveal melanomas with an average follow-up of 36 months. Of these, 14 had confirmed metastasis. Allelic imbalance/loss of heterozygosity was studied using microsatellite markers on chromosome 3 enriched in markers located in the previously reported smallest regions of deletion overlap. Chromosomal alterations were assessed by conventional cytogenetics or comparative genomic hybridization (CGH) in a subset of patients. Utilizing genotyping, partial chromosome 3 alteration was detected in 14/47 tumors (30%). In the 23 tumors with available cytogenetic/CGH, partial chromosome 3 alteration was detected in 8/23 (38%) and was caused by both gains (4/8) and losses (4/8) of chromosome 3 with high frequency of complex chromosome 3 aberrations detected by cytogenetics. Out of the 14 tumors with confirmed metastasis, only 1 showed partial chromosome 3 alteration and the remaining showed monosomy 3. By limiting the aggressive disease marker to monosomy 3, genotyping showed 93% sensitivity and 67% specificity for detection of aggressive uveal melanoma. In conclusion, partial chromosome 3 alterations are common in uveal melanoma and mostly caused by complex cytogenetic changes leading to partial gains and/or partial losses of chromosome 3. Partial chromosome 3 alteration is not likely to be associated with highly aggressive uveal melanoma that metastasizes within the first 3 years after treatment. Microsatellite-based genotyping of chromosome 3 is highly sensitive for detection of aggressive uveal melanoma.
authors.affiliation: Department of Ophthalmology, Ohio State University, Columbus, OH, USA. Mohamed.abdel-rahman@osumc.edu
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Abdel-Rahman
authors.forename: Benjamin N
authors.initials: BN
authors.lastname: Christopher
authors.forename: Mohammed F
authors.initials: MF
authors.lastname: Faramawi
authors.forename: Khaled
authors.initials: K
authors.lastname: Said-Ahmed
authors.forename: Carol
authors.initials: C
authors.lastname: Cole
authors.forename: Andrew
authors.initials: A
authors.lastname: McFaddin
authors.forename: Abhik
authors.initials: A
authors.lastname: Ray-Chaudhury
authors.forename: Nyla
authors.initials: N
authors.lastname: Heerema
authors.forename: Frederick H
authors.initials: FH
authors.lastname: Davidorf
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005260:Female; D005838:Genotype; D049670:History, 17th Century; D006801:Humans; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction; D014604:Uveal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*