Investigating How Childhood Tumours and Congenital Disease Develop

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 diseases (that is, abnormalities that children are born with).

The aim of this study is to define exactly which DNA errors underpin childhood tumours and congenital diseases.

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Key information

Conditions

Childhood Tumor Congenital Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Neoplasms

Sex eligibility

All sexes

Study type

Observational

Primary location

Wellcome Sanger Institute

Cambridge, United Kingdom

About this study

Cancers and some congenital anomalies are caused by changes (mutations) in the genetic code (DNA) of cells. The use of Next Generation Sequencing (NGS) has enabled the study of the genetic changes that underpin these diseases, genome wide and at base pair resolution.

A key question about the molecular pathogenesis of a range of childhood tumours and congenital anomalies that remains unanswered is the order in which the different mutations arise. To define the order in which mutations arise, the investigators will need to reconstruct the life history of individual tumours / anomalies. This can be achieved by segregating the major clone ('ancestral' cell) from sub-clones or by studying multiple areas from the same lesion. Although this approach allows timing of mutations to some degree, in childhood tumours and congenital lesions this approach is fundamentally limited by the inability to define embryonic mutations. The basis of the limitation is that the lesions in question is conventionally compared to the patient's germline (the genetic information they have from birth). In such a comparison embryonic mutations will be misclassified as either germline or somatic (acquired).

To overcome this limitation one would have to compare the lesion to the parental germline.

Thus, here this study proposes to perform the first NGS study of childhood tumours and congenital anomalies, focusing on defining the embryonic pathogenesis. A unique feature of this study will be that lesions will be compared to the parental germline to define embryonic mutations. A focus of the analysis will be to define order in which mutations arise.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Presence of childhood tumour / congenital disease, or relative of participant with childhood tumour / congenital disease
Sufficient 'surplus to diagnostic/clinical use' tissue is available
Child assent and parental/guardian consent obtained where applicable

Exclusion criteria

Insufficient surplus tissue is available

Treatment and study plan

Sample collection

Other

Surplus material from surgery. New or stored blood or saliva. Semen (from adult males).

Seeking consent and assent

Other

Consent or assent from all participants to be included in the study. Consent from parent / guardian for inclusion of children in study (as primary participant or relative/sibling, as applicable).

Primary outcomes

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

Time frame: 9.5 years

For each tumour a catalogue of mutations will be derived from sequencing reads. The catalogues will be compared across tumour types / anomalies to identify the mutations that drive individual tumour types / anomalies. The life history of each tumour / anomaly will be determined.

Methylation data will be analysed to derive a methylation profile for each tumour. The profiles of individual tumours will then be compared with each other to see whether tumour-type specific methylation profiles exist.

Sponsors and collaborators

Lead sponsor

The Wellcome Sanger Institute

Other

Registry information

Important dates

Study start: 2017
Primary completion: 2026
Study completion: 2026
First posted: Sep 5, 2024
Registry last updated: Sep 5, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed