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Identification of regulators of metastasis
Dr Sarah Lake
Prof. Sarah Coupland
Prof. Bertil Damato
Collaborators:
Dr Azzam Taktak
Prof. Neil Hall
Summary
To identify the genes on chromosomes 3 and 8q that regulate the spread of uveal melanoma cells to the liver.
Genetic prognostic testing is used routinely at the LOOC to identify those patients with a uveal melanoma that is likely to spread, usually to the liver. This test is based the strong association of the loss of one copy of the third largest chromosome, number 3, and the gain of an area known as the q arm of chromosome number 8 with the spread of melanoma cells from the eye. Chromosomes are the structures that carry our genes and therefore changes in the number of chromosomes in a cell, alters the number of genes (see Figure 1). It is therefore, vitally important to understand why changes in chromosome 3 and 8q genes are so dangerous for uveal melanoma patients.
Affymetrix SNP 6.0 microarray: a high-resolution method that analyses 1.8 million genes across the human genome (see figure 2).
Whole exome “next generation” sequencing.
Using both techniques together we will be able to identify changes in the number of genes present in the uveal melanoma cells and smaller changes in the sequences of the genes, that may also influence the ability of the cells to move away from the eye.
In this study we will compare the genes in uveal melanoma cells that have spread from the eye with those that have not, and in doing this identify the key genetic changes that are regulating the spread of melanoma cells. We will then investigate why and how these genetic changes are so harmful to uveal melanoma patients.
By identifying the genes that drive uveal melanoma spread we hope to determine the best therapies to prolong life in patients with this cancer.
Prof. Sarah Coupland
Prof. Bertil Damato
Collaborators:
Dr Azzam Taktak
Prof. Neil Hall
Summary
To identify the genes on chromosomes 3 and 8q that regulate the spread of uveal melanoma cells to the liver.
Genetic prognostic testing is used routinely at the LOOC to identify those patients with a uveal melanoma that is likely to spread, usually to the liver. This test is based the strong association of the loss of one copy of the third largest chromosome, number 3, and the gain of an area known as the q arm of chromosome number 8 with the spread of melanoma cells from the eye. Chromosomes are the structures that carry our genes and therefore changes in the number of chromosomes in a cell, alters the number of genes (see Figure 1). It is therefore, vitally important to understand why changes in chromosome 3 and 8q genes are so dangerous for uveal melanoma patients.
Affymetrix SNP 6.0 microarray: a high-resolution method that analyses 1.8 million genes across the human genome (see figure 2).
Whole exome “next generation” sequencing.
Using both techniques together we will be able to identify changes in the number of genes present in the uveal melanoma cells and smaller changes in the sequences of the genes, that may also influence the ability of the cells to move away from the eye.
In this study we will compare the genes in uveal melanoma cells that have spread from the eye with those that have not, and in doing this identify the key genetic changes that are regulating the spread of melanoma cells. We will then investigate why and how these genetic changes are so harmful to uveal melanoma patients.
By identifying the genes that drive uveal melanoma spread we hope to determine the best therapies to prolong life in patients with this cancer.
Figure 1. The 46 chromosomes in a normal human cell The DNA regulating all the biological activities of the body is divided into discrete units called genes that are housed in 23 pairs of chromosomes. These are recognised by their shape and numbered according to their size. The common genetic changes associated with spread of the tumour cells in uveal melanoma occur in chromosomes 3 and 8. (Image courtesy of the Genetics Home. Reference website http://ghr.nlm.nih.gov/handbook/illustrations/normalkaryotype)
Figure 2. Diagram showing chromosomes 3 and 8 of the human genome in uveal melanoma cells
This data was generated from Affymetrix SNP 6.0 microarray analysis of uveal melanoma cells that had spread from the eye. Blue stripes to the right of chromosome 3 indicate regions of the chromosome that are deleted. Red stripes to the right of chromosome 8q indicate gains of the chromosome.
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