Investigating How Childhood Tumours and Congenital Disease Develop

NCT ID: NCT06584877

Last Updated: 2024-09-05

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Total Enrollment: 600 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-02-02
• Study Completion Date: 2026-02-28

Brief Summary

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.

Detailed Description

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.

Conditions

Childhood Tumor; Congenital Disorders

Study Design

• Observational Model Type: FAMILY_BASED
• Study Time Perspective: OTHER

Study Groups

Research participant with tumour or congenital condition

The participant identified to have a tumour or congenital condition (a condition from birth) that is likely to be due to errors of the genetic code (DNA).

sample collection

Intervention Type: OTHER

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

Seeking consent and assent

Intervention Type: 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).

Relatives

parents, siblings or close relatives of the participant with the tumour or congenital condition.

sample collection

Intervention Type: OTHER

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

Seeking consent and assent

Intervention Type: 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).

Interventions

sample collection

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

Intervention Type: OTHER

Seeking consent and assent

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).

Intervention Type: OTHER

Eligibility Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The Wellcome Sanger Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sam Behjati, PhD

Role: PRINCIPAL_INVESTIGATOR

The Wellcome Sanger Institute

Locations

Wellcome Sanger Institute

Cambridge, , United Kingdom

Countries

United Kingdom

Other Identifiers

207523

Identifier Type: -

Identifier Source: org_study_id