Using HDGC to build a toolkit to distinguish indolent from consequential early cancer lesions

Using HDGC to build a toolkit to distinguish indolent from
consequential early cancer lesions

Lead 1: Prof David Wedge, University of Manchester

Lead 2: Prof Rebecca Fitzgerald, University of Cambridge

Project Summary

Understanding the factors that cause normal cells to become cancerous is crucial in developing tools to
detect tumours before they become incurable. Our current understanding of how cancers form is that the
accumulation of DNA changes triggers a cell to behave like a cancer. Recently, several researchers
including ourselves have identified, surprisingly, that a large number of these changes occur within normal
cells in healthy people with no cancer history. It therefore remains unclear which changes best identify
tissue that is going to become lethal cancer.

Hereditary diffuse gastric cancer (HDGC) is the ideal condition to study this. Patients with HDGC develop
many small changes in the stomach some of which turn into lethal cancers and some of which don’t.
Cambridge has established a unique collection of material donated by patients with this condition. We will
study DNA from their normal stomach and stomach pre-cancers. As DNA changes may not be the only
factor driving these changes we will also look at the cells surrounding the different stages of the disease to
see how these change. We hope to identify those changes that are only seen in high-risk patients and so
could be used to predict who will develop lethal cancer and target them for intervention to prevent this e.g.
early surgery or enhanced follow-up.