Somatic mutation in chronic liver disease

• Research type

  Research Study

• Full title

  Understanding the evolution of the somatic mutational landscape in chronic liver disease across aetiologies and disease stages

• IRAS ID

  346024

• Contact name

  Inigo Martincorena

• Contact email

  im3@sanger.ac.uk

• Sponsor organisation

  Wellcome Sanger Institue

• Duration of Study in the UK

  2 years, 0 months, 1 days

• Research summary

  Deaths from chronic liver disease are rising in the UK and around the world. The leading causes are alcohol-related liver disease, metabolic-dysfunction associated steatotic liver disease (MASLD, formerly known as ‘non-alcoholic fatty liver disease’) and viral hepatitis. Chronic liver disease puts people at significantly increased risk of liver cancer, which in the UK has a 5 year survival of under 15%.
  We understand very little about how liver cells acquire genetic changes, called somatic mutations, as they progress from healthy cells, to disease, to cancer development. This study aims to investigate these somatic mutations across different causes of chronic liver disease, and different stages of liver disease. We hope this will help us to understand how different insults to the liver put the liver cells under different pressures, resulting in varying genetic changes. By understanding these changes specific to disease aetiology and stage, we hope to identify novel genetic targets to focus research in identifying specific prognostic, diagnostic and therapeutic tools in chronic liver disease, and improve outcomes for patients.

  All samples used in this research will have been previously collected by our clinical collaborators with informed consent and local ethical approval where part of a research study. Tissue will have been obtained surplus to clinical requirement, where patients were undergoing liver biopsy, liver resection or liver transplantation (tissue sampling from explanted liver). Therefore patients will not undergo any additional intervention as part of this study.

  This will be a multi-centre study, initially between The Wellcome Sanger Institute and University of Texas Southwestern but may form further collaborations as the study progresses. We hope to complete this study within 2 years as it forms part of a 3-year clinical PhD project.

• REC name

  London - Camberwell St Giles Research Ethics Committee

• REC reference

  24/PR/0838

• Date of REC Opinion

  9 Jul 2024

• REC opinion

  Favourable Opinion