Somatic Mutations in normal and abnormal human cells (Utrecht) (IRAS 234839)

Every cell in our bodies picks up DNA changes over time, and some of these changes can contribute to ageing, disease and cancer. We will map these genetic changes across many different tissues by analysing donated biopsy samples from healthy and diseased organs using modern DNA sequencing. By identifying the mutations present and tracing how cells are related to one another, we can uncover how our bodies develop, age and sometimes become cancerous. Our findings could improve our understanding of human development, disease processes and the origins of cancer, helping to guide future healthcare and research.

All cells in the human body acquire somatic mutations throughout life. Using modern DNA sequencing technologies, we will analyse pre-collected tissue biopsy samples from multiple organs and anatomical sites, including samples from normal tissues and cancer or disease states obtained post mortem. Samples will be sourced from donors recruited to the Somatic Variation Bodymap study at the University Medical Centre Utrecht and from commercial suppliers.

We will identify and characterise somatic mutations across different cell types, including cancer-associated driver mutations, to understand the number, types and underlying mutational processes responsible for their accumulation. Sequence data will also be used to reconstruct cell lineage trees, enabling investigation of embryonic development, the contribution of embryonic cells to adult tissues, developmental disorders, ageing and the shared ancestry of adult tissues. This work will provide fundamental insights into somatic mutagenesis, human development, ageing and cancer development.

Rationale

This study will provide insights into the fundamental processes of somatic mutagenesis, ageing and cancer development and the pattern and burden of somatic mutations that contribute to disease processes will inform on potential therapeutic targets.

Aims

The study aims to:

• use somatic mutations to reconstruct cell lineages, including normal development of the human embryo and of individual organs, abnormal human development, and the evolving structure of cell populations in adult tissue.

Primary Outcome

The study will measure the burden and prevalence of somatic mutation and mutational signatures in normal and
cancer samples.

Key Secondary outcome(s)

None

Study Type

Observational

Participant and Sample Information

Populations involved:

Individuals from whom samples were collected post mortem for the University Medical Centre Utrecht or collected by commercial suppliers based in the UK.

Countries of recruitment:

International

Approximate participant or sample numbers (if applicable):

500

Key inclusion criteria:

This study will include pre-collected samples from donors to the Department of Anatomy, University Medical Centre Utrecht and samples from commercial suppliers.

Key exclusion criteria:

Any sample not from a donor to the Department of Anatomy, University Medical Centre Utrecht or samples not available from commercial suppliers

Recruitment status:

Non-recruiting: Pre-collected samples 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 London – Surrey NHS Research Ethics Committee. The study received REC approval on 26 October 2017.

IRAS 234839

REC reference: 17/LO/1801

Data and Sample Use

Data sharing:

Anonymised DNA sequence data are stored in the European Genome-Phenome Archive (EGA) and made available to bonafide 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 the relevant scientific programme at mrs@sanger.ac.uk.

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