Uveal melanoma is the most common primary intraocular malignant tumour in adults. Despite improvements in the diagnosis and treatment of the primary tumour, patients continue to have the same mortality rate as several decades ago, reflecting our poor understanding of the mechanisms behind the formation of metastases in this disease. The purpose of this study was therefore to characterize an animal model of uveal melanoma and use this model to study the transcriptional changes that cells undergo from culture to intraocular tumour, to circulation and finally to the formation of a metastatic nodule. / Using microarrays we identified 314 changes in transcript abundance between the intraocular tumour and metastatic lesions. Principal Components Analysis was used to cluster these transcripts into four distinct groups. A further 61 gene transcripts showed statistically significant changes between re-cultured cells isolated from the model, with the circulating malignant cells representing an intermediate step between cells isolated from intraocular tumours and metastatic lesions. We have produced a detailed analysis of the molecular changes that take place as human uveal melanoma cells evolve from a primary tumour to metastasis in an animal model, including the decrease in expression of specific melanoma markers. These changes were verified using quantitative real time polymerase chain reaction and three different functional assays. / In addition we sought to describe the genetic changes that are present in these cells. Using comparative genomic hybridization arrays we were able to successfully describe the deletions and amplifications that are present in genomic DNA extracted from paraffin embedded sections of the primary tumour. This represents the first time that archival tissue has successfully been used for this sort of analysis in uveal melanoma. We identified several genomic amplifications and deletions including an area of amplification of Wnt2, which is involved in beta-catenin regulation and C-Met, which plays a role in tumour cell homing to the liver in patients. / To the best of our knowledge, this is the first time that a detailed genetic analysis has been carried out on the progression of uveal melanoma from intraocular tumour, to circulation, to the formation of metastases.

No description available.

No description available.

No description available.

Microarray expression analysis was carried out to identify genes with a role in epithelial ovarian cancer (EOC). The U133A Affymetrix GeneChipRTM was used to determine the expression patterns of the 3p25.3-ptel genes represented on the microarray in 14 primary cultures of normal ovarian surface epithelial (NOSE) samples, 25 frozen malignant ovarian tumor samples and four EOC cell lines. Seven genes with differential expression patterns in the tumor samples compared to the NOSE samples were identified as candidates for further analysis, starting with ARPC4, SRGAP3 and ATP2B2. Although none of the candidates had been previously studied in ovarian cancer, several had either family or pathway members that had. Expression patterns seemed unaffected by either tumor histopathological subtype or the allelic imbalances observed with loss of heterozygosity (LOH) analysis. The absence of association with genomic context suggested that differential expression was the result of transcriptional regulation rather than direct targeting.

No description available.