When: Wednesday, September 7, 2022, 12:00 PM - 1:30 PMWhere: Perrin Lecture Theatre, Blizard Institute, Whitechapel
Speaker: Dr Matthew Hoare - University of Cambridge and CRUK Cambridge Centre
Title: Why do patients with liver disease get cancer?
The next session of our Institute Research Seminar Series will take place on Wednesday 7 September, 12.00-1.30pm, at the Perrin Lecture Theatre, Blizard Institute. Dr Matthew Hoare from the University of Cambridge and CRUK Cambridge Centre will present “Why do patients with liver disease get cancer?"
We would encourage everyone to attend this seminar and look forward to seeing as many of you there as possible. Snacks and refreshments will also be provided after the seminar. Please register as soon as possible so that we have an idea of numbers for the catering order.
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. 90% of HCC develops in patients with chronic liver disease (CLD); the causes of CLD are changing, with rapidly rising obesity and type 2 diabetes driving non-alcoholic fatty liver disease (NAFLD). Patients with CLD form a clear at-risk population for HCC development, potentially amenable to early detection. The liver in CLD is marked by a cancerisation field effect; however, the biological substrate of this field effect is unknown.
We hypothesised that this field effect could be encoded at HCC-associated genomic loci. We used whole genome sequencing of non-malignant human CLD tissue but did not find HCC-associated driver mutations. We identified recurrent functional somatic mutations in several disease-relevant metabolism genes, with evidence of convergent evolution in the same liver, suggesting overwhelming selective advantage. On-going work is exploring the functional relevance of these somatic mutations upon progression of systemic metabolic dysfunction and hepatic carcinogenesis.