Publications by authors named "Sarah Tadhg Ferrier"

2 Publications

  • Page 1 of 1

Novel Methylation Patterns Predict Outcome in Uveal Melanoma.

Life (Basel) 2020 Oct 20;10(10). Epub 2020 Oct 20.

Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.

Uveal melanoma (UM) is the most common intraocular tumor in adults. Despite effective local treatments, 50% of patients develop metastasis. Better ways to determine prognosis are needed as well as new therapeutic targets. Epigenetic changes are important events driving cancer progression; however, few studies exist on methylation changes in UM. Our aim was to identify methylation events associated with UM prognosis. Matched clinical, genetic, and methylation data for 80 UM cases were obtained from The Cancer Genome Atlas (TCGA). Top differentially methylated loci were sorted through hierarchical clustering based on methylation patterns, and these patterns were compared to tumor characteristics, genomic aberrations, and patient outcome. Hierarchical clustering revealed two distinct groups. These classifications effectively separated high and low-risk cases, with significant differences between groups in patient survival ( < 0.0001) and correlation with known prognostic factors. Major differences in methylation of specific genes, notably , , and , were also seen. The methylation patterns identified in this study indicate potential novel prognostic indicators of UM and highlight the power of methylation changes in predicting outcome. The methylation events enriched in the high-risk group suggest that epigenetic modulating drugs may be useful in reducing metastatic potential, and that specific differentially methylated loci could act as biomarkers of therapeutic response.
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http://dx.doi.org/10.3390/life10100248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589184PMC
October 2020

Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation.

Cancers (Basel) 2020 Oct 11;12(10). Epub 2020 Oct 11.

Cancer Research Program, Research Institute of the McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada.

Extracellular vesicles (EVs) carry molecules derived from donor cells and are able to alter the properties of recipient cells. They are important players during the genesis and progression of tumors. Uveal melanoma (UM) is the most common primary intraocular tumor in adults and is associated with a high rate of metastasis, primarily to the liver. However, the mechanisms underlying this process are poorly understood. In the present study, we analyzed the oncogenic potential of UM-derived EVs and their protein signature. We isolated and characterized EVs from five UM cell lines and from normal choroidal melanocytes (NCMs). BRCA1-deficient fibroblasts (Fibro-BKO) were exposed to the EVs and analyzed for their growth in vitro and their reprograming potential in vivo following inoculation into NOD-SCID mice. Mass spectrometry of proteins from UM-EVs and NCM-EVs was performed to determine a protein signature that could elucidate potential key players in UM progression. In-depth analyses showed the presence of exosomal markers, and proteins involved in cell-cell and focal adhesion, endocytosis, and PI3K-Akt signaling pathway. Notably, we observed high expression levels of HSP90, HSP70 and integrin V in UM-EVs. Our data bring new evidence on the involvement of UM-EVs in cancer progression and metastasis.
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http://dx.doi.org/10.3390/cancers12102923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600758PMC
October 2020