iSITE: Investigation of Somatic alterations in Tumours of the Eye
Research type
Research Study
Full title
iSITE: Investigation of Somatic alterations in Tumours of the Eye
IRAS ID
242945
Contact name
Pui Ying Chan
Contact email
Sponsor organisation
Genome Research Ltd
Duration of Study in the UK
2 years, 11 months, 30 days
Research summary
Research Summary:
Uveal melanomas are rare cancers that arise from pigment cells (melanocytes) in the eye. Like most rare cancers, limited interest in developing new therapies and a lack of clinical trials contributes towards relatively worse survival rates compared with common cancers. Following treatment of uveal melanoma with either surgical removal of the eye (enucleation) or local radiation (plaque brachytherapy), approximately half of all patients will develop metastases (new tumours). Most patients will die within a few months despite current therapies.
Conjunctival melanomas (cancer of the surface of the eye which lines the inside of the eyelids) are an extremely rare subset of eye cancers which also have poor survival outcomes once metastasised.
Modern DNA sequencing technologies enable researchers to identify mutations acquired during the lifetime of an individual (these are known as somatic mutations). Some of these somatic mutations occur in cancer-associated genes, and increase the risk of developing cancer. This study will use sequencing technologies to look to identify mutations associated with cancers of the eye. By sequencing at different stages of the disease we hope to build a timeline of the order of mutations that occur during eye cancer development. We will also generate cell line models to try and understand how these cancers develop, spread (metastasise) and respond to treatments.
We will also look at which somatic mutations are detectable in blood. Blood samples will be collected regularly from participants and circulating tumour DNA, (ctDNA, fragments of DNA released by tumours into the bloodstream) will be sequenced. We will determine whether the mutations present in ctDNA can be used as an indicator of disease progression.
This study will provide much needed insight into a rare and understudied cancer type, with the aim of improving the survival of patients by identifying key mutations to develop novel therapies against.Lay Summary of Results:
A comprehensive map of cell types related to uveal melanoma, normal eye and normal liver tissue was generated through integration of multiple single-cell RNA-seq datasets. This was applied as a reference framework for cell type deconvolution in each of the primary and metastatic uveal melanoma spatial samples. The generated spot level map of tissue architecture have been investigated to uncover underlying cell type niches, guided by anatomical annotation of the samples and delineation of regions of interest by pathologists. Additional analysis of these samples has investigated spot level copy number differences and ligand-receptor interactions, further enhancing our understanding of the spatial distribution and interaction of cell types within the studied tissues.
REC name
London - Bromley Research Ethics Committee
REC reference
18/LO/1350
Date of REC Opinion
30 Aug 2018
REC opinion
Favourable Opinion