Exploring mutational signatures in humans
Research type
Research Study
Full title
Exploring the biological processes underlying mutational signatures identified in patients with inherited disorders and in patients exposed to mutagens
IRAS ID
116993
Contact name
Serena Nik-Zainal
Contact email
Sponsor organisation
Genome Research Ltd.
Duration of Study in the UK
4 years, 0 months, 1 days
Research summary
Recently, my colleagues and I searched for every mutation in the DNA of breast cancers from 21 women. Using computer-based tools we showed that many patterns exist in breast cancers which were not appreciated before. However, our knowledge and understanding of these mutation patterns is limited. In this project, we aim to understand how and why mutation patterns are generated and whether these patterns occur because of internal or externally arising DNA damage or because the essential DNA repair toolkit in the cell is awry. Because some people are born with naturally occurring defects in genes involved in repair of DNA, these patients provide a rare insight into the mutation patterns that can arise in human beings.
Patients with inherited DNA repair/replication disorders and patients with a history of strong exposure to DNA damaging agents will be recruited and consented into this study by staff at clinical genetics services in the UK and around the world. Linked anonymised blood and saliva samples and skin biopsies will be taken from these patients and sent to the Wellcome Trust Sanger Institute for whole genome sequencing to explore the biological basis of DNA damage and repair signatures.
A resource of linked anonymised induced pluripotent stem cells (iPSCs) and/or lymphoblastoid cell lines (LCLs) from the patients will be established to study mutational patterns under different experimental conditions.
Ultimately, but outside the scope of this current study, data will be compared to mutational signatures extracted from large-scale sequencing of cancer genomes, giving us insight into the perturbations that happen during cancer development.
REC name
East of England - Cambridgeshire and Hertfordshire Research Ethics Committee
REC reference
13/EE/0302
Date of REC Opinion
20 Nov 2013
REC opinion
Further Information Favourable Opinion