Comparison of cytogenetic and molecular genetic tools to ascertain prognostic chromosomal aberrations in uveal melanoma

Loss of chromosome 1p and chromosome 3 are related with metastatic disease and survival in uveal melanoma (UM) patients. Routinely we employ FISH, using either fixed tumour cells or paraffin sections, to determine loss or gain of specific chromosomal regions. The aim of this study was to examine whether SNP arrays can replace FISH to detect prognostic genetic markers. We used tumour DNA from a primary UM cell line and four of its liver metastases and tested these samples on different platforms. Cytogenetic and FISH data were available from previous studies and DNA extracted of the same passage was assayed on Illumina Cyto12 SNP-arrays. Results obtained by SNP-array were visualized with the Nexus software package. In the primary UM cell line, M-FISH confirmed the complex karyotype. This cell line and the metastatic cell lines harbour distinct copy number changes on chromosome 3 and 8. Loss of heterozygosity (LOH) accompanied with an apparent normal copy number (copy neutral LOH) could easily be detected. However, for a proper quantification of absolute copy numbers detected by SNP-array, additional FISH is essential. The use of array technology is superior in detecting genetic aberrations in UM and can be used for selection of UM patients eligible for future adjuvant systemic therapy. FISH appears a more suitable method for quantification of the exact copy number status. Therefore, the choice for one of the other (molecular) cytogenetic tests should be based on the desired outcome/format of results.