In late 2012, the then Prime Minister, David Cameron, announced the 100,000 Genomes Project.
Its four main aims were;
- to enable new scientific discovery and medical insights
- to bring benefit to patients and set up a genomic medicine service for the NHS
- to create an ethical and transparent programme based on consent
- and to kick start the development of a UK genomics industry.
Genomics England, a company wholly owned and funded by the Department of Health & Social Care, was set up to deliver this flagship project and sequence 100,000 whole genomes from NHS patients, something that, at the time, no one in the world had even attempted.
The project focused on people with cancer and those diagnosed and living with a rare disease and their families.
The first samples for sequencing were to be taken from patients living in England with discussions taking place with Scotland, Wales and Northern Ireland about potential future involvement.
Why cancer and rare disease?
In 2011, almost 160,000 people, in the UK, died from cancer – with over 330,000 new cases reported.
Cancer is more likely to occur as people get older and, as a consequence of this, predictions suggest that the number of cancer cases will rise as people live longer.
And although rare diseases are individually very uncommon (there are between 5000 and 8000 of them), a surprisingly large number of people are affected in total – about 3 million – that is one in 17 of the UK population (nearly 7%).
Genomics has great potential for both because both rare disease and cancer are strongly linked to changes in the genome.
Cancer begins because of changes in genes within what was a normal cell. Although a cancer starts with the same DNA as the patient, it develops mutations or changes which enable the tumour to grow and spread. By taking DNA from the tumour and DNA from the patient’s normal cells and comparing them, the precise changes are detected. Knowing and understanding them strongly indicates which treatments will be the most effective. Genomics has already started to guide and inform doctors about the best treatment for individual patients. Many cancer types, including those for whom there is hardly any successful current treatments such as lung cancer could be helped if only we knew which gene changes were important.
At least 80 percent of rare diseases are genomic with half of new cases found in children. Knowledge of the whole genome sequence may identify the cause of some rare diseases and help point the way to new treatments for these devastating conditions – vital progress given that some rare diseases take two or more years just to identify. As most rare diseases are inherited, the genomes of the affected individual (usually a child) plus two of their closest blood relatives were included to pinpoint the cause of the condition.
In all, it was anticipated that about 75,000 people would be involved. Recruitment of participants to the 100,000 Genomes Project was completed in 2018, with the 100,000th sequence achieved in December 2018.
So where are we now?
2012 – UK government announces 100,000 Genomes Project
2013 – first multi-gene sequencing diagnostic test for tumour profiling in the NHS
2015 – first patients enrolled in 100,000 Genomes Project receive diagnoses
2017 – release of genome-wide genotype data on all 500,000 UK Biobank participants
2018 – 100,000 Genomes Project reaches its target of 100,000 whole genomes sequenced
2020 – first 50,000 UK Biobank participants receive a whole genome sequence
2020 – the UK Government published Genome UK, a vision for the next ten years of genomic healthcare
2020 – routine use of whole genome sequencing in the NHS
Research in the 100,000 Genomes Project (GeCIPs)
More than 2500 researchers and clinicians are collaborating to continue ongoing analysis of data from the 100,000 Genomes Project. They have joined the Genomics England Clinical Interpretation Partnership (GeCIP), forming ‘domains’.
The aim of GeCIP is to help us better interpret genomic data, which will lead to better clinical understanding and better patient outcomes.
Each domain will work on improving the clinical application and interpretation of the data in the 100,000 Genomes Project. They will also carry out research to:
- improve our understanding of genomic medicine and its application to healthcare
- improve our understanding of disease
- lead the way to developing new diagnostics and treatments.
38 GeCIP domains have now had their research plans approved by the Access Review Committee and one of those 38 is “Neuroendocrine Neoplasms”
The objectives of the Neuroendocrine Neoplasms (NENs) GeCIP are:
1. To collect and sequence germ-line and tumour DNA from up to 150 patients with associated clinical data from NEN patients recruited through routine clinical care pathways.
2. To describe common patterns of genomic alterations of well and poorly differentiated NEN tumours independent of their anatomical origin.
3. To describe distinct patterns of genomic alterations between morphologically poorly and well-differentiated tumours; according to Ki67 and anatomical origin.
4. To develop novel prognostic biomarkers and potential predictive biomarkers for systemic treatments.
5. To identify mutational signatures common to NENs and gain further insights into the spectrum of tumour mutational burden in these tumours.
6. To identify novel germ-line variants that may predispose to NENs
7. To confirm the functional effect of appropriate variants using in vitro studies.
NEN (Neuroendocrine Neoplasms) GeCIP sits primarily within the Oncology Arena – in this context it therefore refers to malignant NENs – in other words Neuroendocrine Cancer.
nb there is also work being undertaken in regards the Rare Disease Arena – looking at NENs as a group of rare diseases.
In Genomics : PART TWO : we’ll be looking at Terminology and Real World application of what has been learned to date