Differential topological accumulation of gastric somatic mutations
Research type
Research Study
Full title
Differential topological accumulation of somatic mutations in normal colorectal, gastric and gastro-oseophageal stem cells and their association with carcinogenesis
IRAS ID
228343
Contact name
Mike Stratton
Contact email
Sponsor organisation
Wellcome Trust Sanger Institute
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
All cancer is ultimately due to changes in DNA that take place in cells of the body during normal life. These are termed somatic mutations as they are not inherited from parents or passed onto offspring. However, if one or more of these changes takes place within or affects a cancer gene then the cell that has acquired the change will proceed to become a cancer cell. One of the aims of this study is to identify the critical genes involved in the development of human cancers, specifically oesophageal, colorectal and gastric cancer, which, when combined, are responsible for more than 1425000 deaths worldwide each year.
For this work we are applying to use pre-collected primary tissue, blood samples, isolated DNA and organoids (three dimensional cell culture models) from oesophageal, colorectal and gastric tissues covering normal to pre-neoplastic stages of cancer, in collaboration with the University of Hong Kong.
Tissue samples and organoids will be micro dissected to isolate individual genetically identical cells (clonal units) from which genomic DNA will be extracted and sequenced. We aim to use the whole genome sequencing to study the mutational load and mutational signature (‘footprint’ left by the mutation and repair process in DNA) in healthy and gastric cancer patients of different ages and from different regions of the gastrointestinal tract.
The sequence data will be used to identify somatic mutations, base substitutions (one base in the DNA sequence is replaced with another), genome rearrangement and copy number signatures (when sections of the genome are repeated, this varies between individuals hence a signature).
The information collected will be used to analyse the mutational burden and signatures in relation to topology, age, risk factors and different stages of tumour progression.REC name
West Midlands - Coventry & Warwickshire Research Ethics Committee
REC reference
17/WM/0295
Date of REC Opinion
31 Jul 2017
REC opinion
Favourable Opinion