Somatic Mutations in Normal and Abnormal Human Cells (IRAS 230984)

Cancer and many age-related diseases develop as DNA changes build up in our cells over time, but we still do not fully understand how these changes arise or affect the body. We will examine tissue samples from many different organs and disease states and use DNA sequencing to map the mutations present in individual cells. By tracing the history of cells throughout the body, we will uncover how tissues develop, age and change over life. Our findings could improve understanding of cancer, ageing and developmental disorders, helping to advance future healthcare and biomedical research.

All human cells acquire somatic mutations throughout life. Using modern DNA sequencing technologies, we can detect these mutations in single cells or small cell populations. We will analyse pre-collected post-mortem tissue biopsy samples from multiple organs and anatomical sites representing both normal and disease states, obtained through the medical donation programme at Memorial Sloan Kettering Cancer Center.

By sequencing cells from different tissues, we will identify and characterise somatic mutations, including potential driver mutations associated with cancer development. We will also use genomic sequence data to reconstruct cell lineage trees, providing insight into embryonic development, the contribution of embryonic cells to adult tissues, developmental disorders, tissue ageing and the shared ancestry of adult cell populations. This work will advance understanding of somatic mutagenesis, 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)

N/a

Study Type

Observational

Participant and Sample Information

Populations involved:

Donors providing post-mortem tissue samples to the MDP tissue bank.

Countries of recruitment:

International

Approximate participant or sample numbers (if applicable):

150

Key inclusion criteria:

Samples from patients who consented to donate tissue samples to MDP tissue bank.

Key exclusion criteria:

Any individual who has not consented to take part in the donation of tissue to MDP tissue bank.

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 East of Scotland Research Ethics Service – REC 1 NHS Research Ethics Committee. The study received REC approval on 27 July 2017.

IRAS 230984

REC reference: 17/ES/0102

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.