Dr Miles Levy and Dr Shailesh Gohil, Leicester
Lead researcher, Dr Miles Levy from the University Hospitals of Leicester NHS Trust is a Consultant Endocrinologist and an Honorary Associate Professor in Endocrinology and Genomic Medicine for the University of Leicester. Dr Levy received £9,919.74 from the 2019 Nick Fayers Fund for MEN1 Research in 2019.
End of Grant Report Lay Summary:
The 2019 Nick Fayers Award has been instrumental in increasing our understanding of the genetics of neuroendocrine tumours and working towards developing circulating cell free tumour-derived DNA (ctDNA) as a biomarker for our patients.
Using a technique called whole exome sequencing, we have detected genetic changes which have occurred within the DNA of 10 patients’ neuroendocrine tumours. These include large areas of DNA where entire chromosomes have either been deleted or copied multiple times to small gene level mutations which are specific to each individual’s tumour.
Over the course of 14 months, we have also collected and stored up to 4 blood samples per patient which we will use for ctDNA detection and tracking. DNA, which is released into the blood steam from any cell throughout the body (cfDNA), has already been isolated from these for use in our next stage.
We are now designing a tool to help us detect ctDNA from the isolated blood cfDNA by using each patient’s gene level tumour mutations as targets to pinpoint. We will track the ctDNA in their serial blood samples and see if ctDNA tracks changes in their tumours thereby acting as a biomarker.
Our next stage also involves extending this work to patients with MEN, who may have genetic changes in their tumours in addition to their inherited MEN mutation.
The eventual aim of this research is to detect early occurrence and recurrence of NETs before abnormalities appear on scans. In MEN, the hope is that we can pick up tumours before they have reached an advanced stage by a simple blood test.
List of Presentations (as at March 2021):
Gohil S, Hastings R, Shaw J and Levy M. Allelic deletion of chromosome 18 is common in intra-abdominal neuroendocrine neoplasms. Endocrine Abstracts (2020) 72 P1 DOI: 10.1530/endoabs.72P5
2020 UK and Ireland Neuroendocrine Tumour Society National Conference 30/11/20-3/12/20: ‘Allelic deletion of chromosome 18 is common in intra-abdominal neuroendocrine neoplasms.’
Gohil S. ‘Local Research in NETs.’ The Leicester Neuroendocrine Tumour Patient Educational Event. Devonshire Place, Leicester. 28/2/20
Gohil S. ‘Cushing’s, Endocrine Tumours and Circulating DNA.’ University Hospitals of Leicester NHS Trust Grand Round, 7/2/20
Gohil S ‘ctDNA in the monitoring of neuroendocrine tumours’. Post Graduate Researchers Seminar, University of Leicester. 12/12/19
Comment from AMEND Research Committee:
“Many of the biomarkers used to diagnose and monitor patients with neuroendocrine tumours have low sensitivity and specificity, hence there is a search for new biomarkers. Circulating tumour DNA (ctDNA) refers to DNA that is released into the bloodstream when tumour cells die in the natural cell cycle. This project seeks to identify gene mutations specific to neuroendocrine tumours and determine if changes in ctDNA levels reflect changes in tumour behaviour. The ultimate aim is to be able to detect early occurrence or recurrence of neuroendocrine tumours through a blood test, before abnormalities appear on scans.”
Dr John Ayuk (Birmingham)