Exploring mutational signatures in iPSCs_v1
Research type
Research Study
Full title
Exploring the biological processes underlying mutational signatures identified in induced pluripotent stem cell-lines (iPSCs) that have been genetically modified or exposed to mutagens
IRAS ID
157776
Contact name
Serena Nik-Zainal
Contact email
Clinicaltrials.gov Identifier
100183/Z/12/Z, Funder's reference number - 2
Research summary
Most human cells acquire mutations in their DNA throughout life. These are called somatic mutations and they occur in normal cells, cancer cells and cells from other diseased tissues. Somatic mutations can cause human diseases, particularly cancer, and may be caused by exposure to factors such as sunlight and tobacco smoke. Each cell contains complex DNA repair machinery that reduces mutation accumulation. When this machinery goes wrong, cells can acquire even more mutations, further contributing to disease development.
Recently, improvements in technologies that read the genetic code have made it possible for the entire genetic code of a human being to be "sequenced", and therefore for every mutation to be detected. Using this sequencing technology, scientists have shown that many different mutation patterns (which we call Mutational Signatures) exist, suggesting that there are many different processes causing them.
In this project, we aim to better understand the causes of mutation patterns and to identify the different patterns resulting from different types of DNA damage.
To answer these questions we plan to modify genes that are associated with DNA repair and replication as well as other disease-associated genes, and use sequencing technologies to look at genetic and other cellular alterations that occur as a result. Similarly, we plan to investigate the effects (cellular and genetic) of exposure to a range of chemicals. We wish to use a model system that will provide information relevant to humans, and therefore plan to use induced pluripotent stem cell-lines (iPSCs) that have been derived from human tissue. We hope that exploring the mutational signatures that result from specific gene alterations, or that occur as a result of specific chemical exposure, will provide valuable insight into the causes of mutational signatures across a diverse set of human genetic diseases.
REC name
North West - Liverpool Central Research Ethics Committee
REC reference
14/NW/1029
Date of REC Opinion
9 Jun 2014
REC opinion
Favourable Opinion