Comparative analysis of microsatellite instability and somatic mismatch repair gene status in Lynch related skin and upper gastrointestinal cancers
Principal Investigator: Dr Neil Rajan
Lynch syndrome (LS) is a genetic cancer predisposition syndrome, characterised by an increased risk of developing a wide variety of tumours, most notably bowel, womb, ovarian, but also urinary tract, stomach and selected skin tumours of the oil glands in the skin. It has been estimated that as many as 1 in every 300 people have a MMR gene defect. Once identified, they can benefit from taking aspirin, which reduces the risk of the most common LS cancers by approximately 50%, and can consider surgical and therapeutic options to minimise cancer recurrence and improve acute care. Importantly, they can also benefit from surveillance programs aimed at early cancer detection.
The current problem this proposal aims to improve is that potential LS patients are being missed when presenting with a type of skin cancer or types of upper gastrointestinal cancers linked to LS. We have developed a rapid, low-cost test that can help detect cancers that will identify patients with potential LS. Here we aim to determine to study its role in cutaneous squamous cell carcinoma, where 45,000 new cases are detected per year in the UK. We also want to study upper gastrointestinal (small bowel) cancers which are less common, but are seen to occur more frequently in LS patients than the general population. We will do this by studying existing archival samples of tissue with genetic tests, and aim to determine how useful this approach is for detecting MMR status in these tumour types. Establishing MMR status in skin tumours will lead to increased detection of LS, with benefits to LS patients and their families.
We propose to study cutaneous SCC and upper gastrointestinal cancers to determine the utility of our highly sensitive MSI assay to detect MMR deficient tumours in a collection of unselected archival sporadic cases, with the aim of assessing the sensitivity and cost effectiveness of this assay to screen for MMR deficient tumours.
- Sections obtained from Novopath and DNA extracted and QC’s (Batch 1/3). Optimisation of assay
- IHC assay established and working in lab
- Targeted MMR gene sequencing assay and MSI+ assay established and data available from batch 1
- Batch 2 and 3 complete; validation IHC done on selected samples
- Data analysis; grant and manuscript development