Genetic and epigenetic changes underpinning rare childhood tumours (IRAS 205455)

Cancer remains one of the leading causes of illness and death, yet we still know very little about many rare childhood cancers. We will study anonymised tumour samples to uncover the DNA changes that drive these diseases and help explain why they develop. By comparing the genetic patterns found in different cancers, we hope to discover clues that could point to new treatments and reveal important insights into cancer more broadly. We will share our findings with researchers worldwide so we can accelerate progress towards better care for children with cancer and improve our understanding of the disease.

Cancer develops through genetic (DNA) and epigenetic changes that alter how cells function and grow. Advances in sequencing technologies now allow detailed analysis of the genetic and epigenetic profiles of tumours, providing insights into the biological mechanisms that drive cancer development.

Many common cancers have been extensively characterised, but rare childhood cancers remain poorly understood. We will analyse pre-collected anonymised tumour samples using DNA sequencing to identify the genetic changes associated with these cancers. This may help identify potential targets for new treatments and improve our broader understanding of cancer biology. The data generated will be shared with the research community to support further research into the causes of cancer and the development of improved therapies.

Rationale

Cancers are caused by changes (mutations) in the genetic code (DNA) of cells. Additionally, cancers may be caused by changes in how the genetic code is regulated (epigenetic changes). Technological advances have made it possible to read (sequence) the genetic and epigenetic profile of tumours. This allows us to explain what drives individual cancers.

Many common cancers have been sequenced, however, rare childhood cancers are poorly understood. It is important to investigate these rare cancers for two reasons. First, it might be possible to identify genes that can be targeted with specific drugs. Thus, children suffering from rare cancers might be offered new treatment options. Second, rare cancers often contain remarkable mutations which have enlightened our understanding of cancer more generally.

Therefore one of my goals is to understand, through DNA sequencing, rare childhood cancers.

A further goal is to study epigenetic changes which may cause cancer but do not change the DNA sequence itself.

There is evidence from previous studies that in development of childhood cancers these epigenetic changes may play a particularly important role.

Aims

The study aims to:

• To define the DNA changes (mutations) encoded in the genes found in rare childhood tumours, aiming to identify
  those changes that cause rare childhood tumours.
• To define the changes in the epigenome of tumours. The epigenome is the code that controls and regulates the
  genetic code. It is encoded in a variety of chemical signals that impact on DNA and RNA.

Primary Outcome

Description of the genetic mutations and the methylation landscape (epigenome) of each tumour.

Key Secondary outcome(s)

N/a

Study Type

Observational

Case-series

Participant and Sample Information

Populations involved:

Individuals diagnosed with rare childhood cancers

Countries of recruitment:

UK

Approximate participant or sample numbers (if applicable):

1250

Key inclusion criteria:

• Rare childhood tumour that has not been previously studied by DNA sequencing.
• Sufficient archival material is available.

Key exclusion criteria:

• Common tumour which may be more easily studied prospectively or rare childhood tumour that has already been
  studied by DNA sequencing.
• Insufficient archival material is present.

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 – Brent NHS Research Ethics Committee. The study received REC approval on 11 May 2016.

IRAS 203519

REC reference: 16/LO/0960

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 sb31@sanger.ac.uk.

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