Comprehensive analysis of gene expression in UM
Research type
Research Study
Full title
Comprehensive analysis of gene expression in uveal melanoma and how this influences functional effectors modulating disease progression and metastasis.
IRAS ID
243718
Contact name
Sarah, E Coupland
Contact email
Sponsor organisation
University of Liverpool
Duration of Study in the UK
2 years, 6 months, 28 days
Research summary
Research Summary
Uveal melanoma (UM) is the most common adult eye cancer and affects 4-6 individuals per million annually. Early diagnosis and treatment with surgery or radiotherapy has a high success rate. Despite this, in 50% of patients the cancer will spread (called metastatic uveal melanoma) from the eye to other organs, in particular the liver. The prognosis for uveal melanoma that has spread is usually very poor and patients do not generally survive longer than 12 months once detected.Once people are diagnosed with UM it is possible to separate those who have a high risk of developing metastatic disease from those with a low risk using characteristics such as the size and shape of the tumour, the patient’s age, the presence/absence of certain gene alterations. A high risk patient will be monitored more frequently to detect metastases as early as possible, however at the moment there is no effective therapy available and few alternative treatment options that can act against these tumours. It is therefore essential to improve our current understanding of why some tumours metastasise and others don’t, and to identify new targets to develop future treatments.
The aim of this study is to look at genes in uveal melanoma samples from low and high risk patients and to identify targets that can be further studied to define their role in the development of metastases and may offer a therapeutic strategy.
Summary of Results
Uveal melanoma (UM) is a rare eye cancer found in adults. In about 50% of patients who develop this disease the cancer cells will spread from the eye to the liver. Once the cancer cells have spread to the liver, there are currently few effective treatments. Patients with specific tumour characteristics including changes in the tumour DNA, are at an increased risk of the eye cancer spreading to the liver; we are able to determine these features and stratify patients into high and low risk groups accordingly.In this study, we used high resolution techniques to analyse the activity of genes and small RNA molecules (miRNAs) in uveal melanoma samples, including data from both our laboratory studies and a public cancer database (The Cancer Genome Atlas). We aimed to find genes and pathways that are abnormally active in UM and could be targeted with existing drugs (a process known as drug repurposing).
We confirmed some of the key findings by testing RNA from UM patient samples using a method called RT-PCR, which measures gene activity. We also analyzed DNA from these samples to identify common mutations in genes known to drive UM.
Finally, we used UM cell lines (lab-grown cancer cells) that represent the genetic changes found in UM patients to test how altering miRNA levels affects the activity of target genes and cancer cell growth.
This work has provided new insights into the genetic and molecular factors driving UM and suggests potential targets for future therapies.
REC name
Yorkshire & The Humber - Sheffield Research Ethics Committee
REC reference
18/YH/0213
Date of REC Opinion
31 May 2018
REC opinion
Favourable Opinion