Exploring the Landscape of Somatic Mutations in Human Tissue

• Conditions: Somatic Mutation
• Interventions: Other: sample collection

• Registration Number: NCT06585800
• Lead Sponsor: The Wellcome Sanger Institute

Brief Summary

Every cell in the human body contains a blueprint of the body called the genome. Throughout life, the genome can become damaged resulting in errors (mutations) that can change the way cells behave and may result in diseases such as cancer. Examining the mutations found the genome of both normal (non-cancerous) and diseased cells can give a valuable insight into the very earliest stages of cancer development.

Comparing the number and type of mutations in different normal tissues is revealing new insights, helping us to better understand more about why cancer develops.

Detailed Description

The investigators are seeking to characterise somatic mutations found in normal human tissue, as well as diseased tissue. These experiments have shown that a number of mutational processes previously observed in cancer cells, may also be present in normal tissues. By further exploring normal tissue samples from across the body, the investigators will be able to better understand why certain organs are more susceptible to mutations and what underlies the mutational processes active in many different tissue types.

Study Timeline

• Study Start: 2019-03-01
• Study First Submitted: 2024-07-04
• Status Verified: 2024-09
• Study First Submitted QC: 2024-09-04
• Last Update Submitted: 2024-09-05
• Study First Posted: 2024-09-06
• Last Update Posted: 2024-09-12
• Primary Completion: 2026-01-31
• Study Completion: 2026-01-31

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 1800

Inclusion Criteria

• Individuals undergoing surgery
• Individuals undergoing invasive procedures, e.g.
• Endoscopy (oesophagogastroduodenoscopy, small bowel enteroscopy, colonoscopy, sigmoidoscopy,proctoscopy) for suspected gastrointestinal disease, e.g. coeliac disease or for surveillance of known conditions/diseases.
• Tissue biopsy - of solid organs
• Prospective sampling will be carried out with the research participants' consent.

Exclusion Criteria

• where consent has not been received

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
1.Undergoing surgery	sample collection	For participants undergoing surgery, research tissue specimens will be sampled from resected tissue - no additional solid tissue research samples will be removed from patients undergoing surgery. Samples taken from surgery will be either from the margins of the resected specimen, or the specimen itself. However this will be done only with agreement with the clinical team and the histopathologist to ensure that clinical pathology is not affected.
2.1. Undergoing Invasive Procedures (Endoscopy)	sample collection	Endoscopy (oesophagogastroduodenoscopy, small bowel enteroscopy, colonoscopy, sigmoidoscopy, proctoscopy) for suspected gastrointestinal disease e.g. coeliac disease or for surveillance of known conditions/ diseases. For participants undergoing endoscopy as part of their routine clinical care, additional tissue biopsies will be taken for the purpose of this study only in cases where it is safe to do so.
2.2. Undergoing Invasive Procedures (Biopsy)	sample collection	Tissue Biopsies of solid organs. For participants undergoing tissue biopsy as part of their routine clinical care, additional tissue biopsies will be taken for the purpose of this study only in cases where it is safe to do so. For those undergoing high risk biopsies, e.g. liver biopsies, samples for research will only be taken from clinical specimens, i.e. no additional specimens will be taken solely for the purpose of research.

Primary Outcome Measures

Name	Time	Method
Comparison of somatic mutation burden	6.25 years	Identify and quantify variations that may contribute to disease development and progression between samples from the same donor and different donors, encompassing both healthy individuals and those with diseases.

Secondary Outcome Measures

Name	Time	Method
Number of Somatic Mutations	6.25 years	Quantification of the total number of somatic mutations present in the tissue samples.
Spectrum of Mutational Signatures	6.25 years	Analysis of the spectrum of mutational signatures, including: * Base Substitutions; * Indels (Insertions and Deletions); * Genome Rearrangements; * Copy Number Changes
Size of Clonal Populations	6.25 years	Measurement of the size of clonal populations within the tissue samples.
Relatedness of Clonal Populations	6.25 years	Analysis of the genetic relatedness of clonal populations within the tissue samples.

Trial Locations

Locations (1)

Wellcome Sanger Institute; 🇬🇧 Cambridge, United Kingdom