Microarray comparative genomic hybridisation analysis of intraocular uveal melanomas identifies distinctive imbalances associated with loss of chromosome 3

Abstract

Defining regions of genomic imbalance can identify genes involved in tumour development. Conventional cytogenetics has identified several nonrandom copy number alterations (CNA) in uveal melanomas (UVM), which include monosomy 3, chromosome 6 abnormalities and gain of 8q. To gain further insight into the CNAs and define the regions involved more precisely we analysed 18 primary UVMs using 1 Mb BAC microarray comparative genomic hybridisation (CGH). Our analysis showed that the most common genomic imbalances were 8q gain (78%), 6p gain (67%) and monosomy 3 (56%). Two distinct CGH profiles could be delineated on the basis of the chromosome 3 status. The most common genetic changes in monosomy 3 tumours, in our study, were gain of 8q11.21 -q24.3, 6p25.1 -p21.2, 21q21.2 -q21.3 and 21q22.13 -q22.3 and loss of 1p36. 33 -p34.3, 1p31.1 -p21.2, 6q16.2 -q25.3 and 8p23.3 -p11.23. In contrast, disomy 3 tumours showed recurrent gains of only 6p25.3 -p22.3 and 8q23.2 -q24.3. Our approach allowed definition of the smallest overlapping regions of imbalance, which may be important in the development of UVM.

Integrative Genomic Analysis of Aneuploidy in Uveal Melanoma

“…This analysis confirmed that 3-and 6p+ represent almost mutually exclusive alterations and thereby provided further support to the idea that 3-and 6p+ signify alternative pathogenetic sequences, as previously suggested (22,25,26). In addition, we identified a third subgroup, representing f18% of all tumors, which were normal for chromosomes 3 and 6p.…”

“…Although other studies have identified discrete patterns of chromosomal alterations in UM (4,12,14,20,22), this study used statistical ''pattern recognition'' techniques to organize chromosomal alterations into significant groupings. This analysis confirmed that 3-and 6p+ represent almost mutually exclusive alterations and thereby provided further support to the idea that 3-and 6p+ signify alternative pathogenetic sequences, as previously suggested (22,25,26).…”

Chromosome 3 Status in Uveal Melanoma: A Comparison of Fluorescence In Situ Hybridization and Single-Nucleotide Polymorphism Array

“…[3][4][5] Of various cytogenetic abnormalities observed, monosomy 3 is the strongest predictor of metastatic risk. [5][6][7][8][9][10][11][12][13][14] Several techniques are currently being used to detect monosomy 3 and other chromosomal changes associated with the development of metastatic disease. Gene-expression profiling is also being used in prognostication.…”

Marked Genomic Differences Characterize Primary and Secondary Glioblastoma Subtypes and Identify Two Distinct Molecular and Clinical Secondary Glioblastoma Entities

“…For primary glioblastoma-specific MCRs, there are 23 gains/amplifications with a median size of 0.87 Mb and median number of 13 genes. Of these 23 loci, 6 represent loci that have been significantly narrowed and 11 loci have not been described in glioblastoma, yet their cancer relevance is reinforced by validated connections to other cancer types such 2p25 in ganglioneuroblastoma (29), 6p25 in uveal melanoma (30), and 17q21 in medulloblastoma (ref. 31; Table 2).…”