Investigating how childhood tumours and congenital anomalies develop (IRAS 207523)

Some children develop tumours or are born with serious health conditions because mistakes occur in their DNA during early development. We want to understand exactly which DNA changes are responsible for these conditions by studying the genetic information that guides how a fertilised egg grows into a human being. By identifying the DNA errors linked to childhood tumours and congenital diseases, we hope to improve our understanding of how these conditions arise and provide knowledge that could support better diagnosis, treatment, and future research.

Human development is directed by genetic information contained within DNA. Errors in the DNA sequence can disrupt normal developmental processes, leading to childhood tumours and congenital diseases.

We will study the genetic changes associated with these conditions to identify the specific DNA errors that underpin their development. Improving our understanding of the genetic basis of childhood tumours and congenital diseases may provide important insights into disease mechanisms and support future advances in diagnosis, treatment, and research.

Rationale

Every cell and every organ in the human body derives from a fertilised egg. As the fertilised egg divides, a human being develops and grows. The process of how the fertilised egg divides and forms a human being is very sophisticated and is directed by the genetic information, the DNA, that is present in every cell.

When errors, mutations, in the DNA code arise, the orderly process of human development can be disrupted. This can lead to the development of tumours during childhood and congenital anomalies (that is abnormalities that children are born with).
The aim of this study is to define exactly the DNA errors that underpin childhood tumours and congenital diseases.

Aims

The study aims to:

• To define the DNA, RNA and methylation changes (mutations) encoded in the genomes of congenital anomalies and childhood tumours.
• To derive the exact sequence of mutations that lead to the development of each condition.
• To determine how mutations affect the initiation and development of congenital diseases and childhood tumours.

Primary Outcome

Description of the genetic mutations of each tumour and congenital anomaly.

Understanding of the effects of the mutations on the development of the childhood tumour or congenital disease.

Key Secondary outcome(s)

N/a

Study Type

Observational

Case series

Participant and Sample Information

Populations involved:

Individuals with childhood tumours and congenital diseases

Countries of recruitment:

UK

Approximate participant or sample numbers (if applicable):

450

Key inclusion criteria:

1) Presence of childhood tumour / congenital disease.
2) Sufficient ‘surplus to diagnostic/clinical use’ tissue is available.
3) Child assent and parental/guardian consent obtained.

Key exclusion criteria:

1) Insufficient surplus tissue is available.

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 28 December 2016.

IRAS 207523

REC reference: 16/EE/0394

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.