SMS – Study of Somatic Mutations Using Genome Sequencing (IRAS 182435)

Exploring how changes in DNA build up in the tissues and cells of people's bodies over time. The study uses DNA sequencing to better understand how factors such as age, environmental exposures, disease history and treatment affect the accumulation of these changes in healthy and diseased tissues.

Disease and tissue ageing are thought to be influenced by genetic changes, known as somatic mutations, that are acquired throughout life. These mutations may arise due to environmental exposures such as ultraviolet light or tobacco smoke, or through errors that occur when cells divide.

By using DNA sequencing to read the genomes of human tissues and cell samples the study seeks to identify and characterise somatic mutations and clusters of cells carrying these mutations, in both normal and diseased tissues. This information will help scientists better understand how mutation burden varies with age, environmental exposure, disease history, and treatment.

Rationale

Somatic mutations arise when DNA damage is not fully repaired and may be passed on to daughter cells, leading to clusters of cells carrying the same mutation within tissues. The number, size, and nature of these clusters may reflect environmental exposures, tissue-specific cell division rates, and biological processes associated with ageing and disease.

Advances in next-generation sequencing technologies now allow the detection of somatic mutations across large numbers of genes in small tissue samples. However, knowledge of how frequently such mutant cell clusters occur in normal and diseased human tissues, and their biological significance, remains limited. This study applies genome sequencing approaches to human samples to improve understanding of somatic mutation patterns across tissues and individuals.

Aims

The study aims to:

• measure the frequency, size, and nature of acquired (somatic) mutations in clusters of cells in normal and diseased tissues.
• assess how somatic mutation patterns vary according to age, environmental exposures, disease history, and treatments such as radiotherapy.
• generate data that will inform the design of future, larger studies investigating the role of somatic mutations in ageing and disease processes.

Primary Outcome

The study will measure the burden of somatic mutations in tissues and how this varies between controls and patients. The specific mutations in genes and their prevalence will be determined.

Key Secondary outcome(s)

None

Study type

Observational (case–control)

Participant and sample information

Populations involved:

Adult patients with potential genetic damage linked to environmental exposures, disease history, or medical treatments, and healthy adult control participants.

Countries of recruitment:

International

Approximate participant or sample numbers (if applicable):

750 participants.

Key inclusion criteria:

Controls: Healthy adults with capacity to consent

Patients: Adults with capacity to consent who have been highlighted by research nurse or clinician as potentially having genetic damage caused by environmental factors, such as UV light or tobacco smoke, or other factors, such as disease history or treatments, for example radiotherapy.

Key exclusion criteria:

Adults who lack capacity to consent.
Children.

Recruitment status:

Recruiting by invitation only.

Governance and Ethical Approval

Governance and oversight:

Study Sponsor: Wellcome Sanger Institute

All work conducted at the Wellcome Sanger Institute is reviewed and overseen by institutional Research Governance processes, ensuring compliance with ethical, legal, and regulatory requirements.

Ethical approval:

This study has been reviewed by the East of England – Cambridge NHS Research Ethics Committee. The study received REC approval on 14 July 2015.

IRAS 182435

REC reference: 15/EE/0218

Data and sample use

Data generated:

Genome sequencing data from germline and tissue-derived samples, catalogues of somatic mutations, and associated analytical outputs.

Data sharing:

Anonymised DNA sequence data are stored in the European Genome-Phenome Archive (EGA) and made available to bona fide researchers via managed access, subject to data access agreements. Anonymised samples and cultured cells may also be shared with other legitimate research organisations under appropriate legal agreements.

IPD sharing statement

Deidentified individual participant-level data (IPD) will not be shared as part of this study.

Completion date

Ongoing

Further information

For enquiries about the scientific aims of this study or potential collaboration, please contact Phil Jones at pj3@sanger.ac.uk.

For enquiries relating to research governance, ethics, or regulatory oversight, please contact the Research Governance team at researchgovernance@sanger.ac.uk.