Supporting the

Neuroendocrine Cancer Community

Research – 100,000 (100K) Genomes Project

Mar 12, 2021

 We were delighted to award the 2020 NCUK grant to Dr Marc Ooft, Consultant Histopathologist, Kings College Hospital.

We would also like to thank Mr P Moxham for his generous donation towards our research grant.

Dr Ooft’s research, alongside the NET GeCIP group, is focusing on ‘Improving patient stratification through epigenetic and tumour microenvironmnet analysis of the 100,000 Genomes project neuroendocrine tumour cohort.’

The 100,000 (100K) Genomes Project was delivered as a transformation project across the NHS and was the largest undertaking of whole genome sequencing (WGS) globally in routine clinical care.

WGS is powerful in that it can identify many genomic aberrations (single nucleotide variants, deletions, insertions, structural variants along with pathogenic viral insertions).

The NET GeCIP was formed to analyse and interpret WGS data produced from 130 NEN cases recruited through the 100K project. Analysis of the cancer arm of 100K genomes legacy data has identified that whole genome sequencing identified a potential therapeutic target or clinical trial in 50% of cancer cases.

It is known that NETs have a very low background mutation rate and few actionable mutations which can guide therapeutic decision making. However, epigenetic alterations are significantly more common than mutations in NETs with DNA methylation found in >70% of NETs in different subsites (Stalberg 2016, Cives 2016).

This proposal sets out to augment the 100K WGS data by performing epigenetic and tumour microenvironment analyses in order to improve patient stratification and potentially identify novel therapeutic approaches.

The Thirlwell group has previously identified molecular subgroups of pancreatic and intestinal NETs based on integrated DNA methylation and transcriptome analyses (Pipinikas 2015, Karpathakis 2016, Karpathakis 2017).

However, there are no studies which have integrated genome-wide methylation patterns of neuroendocrine tumours with WGS. Furthermore, few studies have also looked at the influence of the tumour micro-environment on the methylation profiles of NETs. The latter is important as the heterogeneous (epi)genetic profiles in NETs at different primary sites might be microenvironment driven and this could also possibly correlate with biological aggressiveness of these tumours.

Through the work outlined in this project genetic and epigenetic correlations with histopathological predictors of malignant behaviour will be determined. Elucidating the gaps and inconsistencies in our (epi)genetic knowledge of NETs will help to improve patient stratification and prognostication.

The 100K project provided infrastructure and funds to recruit 17,000 cancer patients and undertake WGS. No funds are available for other genomic analyses of these cases. However, DNA has been extracted and stored which will be utilised for the DNA methylation analysis outlined in this proposal.

Within the NET GeCIP there is expertise in WGS and the infrastructure to define the immune landscape in NETs through histopathological and DNA methylation analyses (MethylCybersort).

The overall aim of this project is to further our understanding of the genetic and epigenetic changes in conjunction with detailed histopathological assessment and clinical annotation. This will lead to future work culminating in the development of standardised genetic and epigenetic markers for NETs to aid prognostication and optimise stratification of patients being considered for novel immunotherapy and other targeted therapies”.

Dr Marc Ooft is a Consultant Cellular Pathologist at Kings College Hospital, he also plays an active role within the South East Genomic Laboratory Hub, contributing to the shaping of pathology services across the region

  • Validity of whole genomes sequencing results in neoplasms in precision medicine Journal of Clinical Pathology (2020)


Healthcare Science Week is an annual week-long programme designed to promote the amazing work of healthcare science professionals and highlight the difference they make to patients lives. This year, it takes place between 5 and 14 March.

Science and technology is vital in modern healthcare and can change lives for the better.

Research is one aspect where science and technology comes together not only to expand our knowledge but also explore new ways of delivering healthcare – whether through improved understanding of ‘the patient experience’ to new advances in knowledge to the development of innovative medicines and technologies.

To celebrate Healthcare Science Week we would like to share with you how your donations have made a number of complex and groundbreaking pilot research projects possible.

(Find out more about our Research Grants and the work your donations help us support here).