Whole Genome Sequencing is a very hot topic and its going to get hotter. There has been recent press coverage about delays in WGS not just for brain cancer, but for other cancers. So this is the beginning of a conversation about which you’ll be hearing so much more. Conversations are growing around what it is, why it is important in decision making, what the current issues are and what’s being done to resolve the challenges. The purpose of this feature is to familiarise you with the key points: we’ll expand on these over the coming weeks.
What is WGS?
Whole-genome sequencing (WGS) is the analysis of the entire genomic DNA sequence of a cell at a single time, providing the most comprehensive characterisation of the genome.
Why is it important?
WGS has revolutionised bioscience and has proven to be essential and invaluable to the identification of gene functions and their involvement in disease. It explores a much larger sequence in comparison to targeted approaches and therefore generates much more information about communities.
Why does it matter to people living with a brain tumour?
A Glioblastoma brain tumour is the most aggressive type of brain tumour. It is described as being heterogeneous which means it is made of various cells which are different. This means that there is more than one mutation of the cancer cell which causes the tumour to grow. Treatments are targeted to the different types of mutations to stop growth, such as IDH1. We know though that over time cells find workarounds to the treatments and mutate, so that the tumour grows again (called progression). If we can map these mutations in detail it gives researchers the opportunity to develop therapies which can target the cancer cells and what causes them to mutate.
What does this mean?
Bottom line? It means that it isn’t going to be one treatment that is needed. We are going to need multiple treatments to target the different mutations. But we need to know what these mutations are and we need to look at cohorts of these tumours as well as individuals so that therapies can be personalised.
What are the challenges?
It’s a complex landscape and the challenges are varied.
In 2018 the Government set a high bar by promising that WGS would be available to all people with rare cancers. Then COVID caused a pivot; key resources were diverted so this has not been achieved.
We know that people diagnosed with a GBM can wait for over 400 days for WGS; this is too long to wait when you are diagnosed with a life limiting cancer. The information given by WGS at this point is out of date and of little use to the person with the GBM.
There isn’t parity of access to tissue frozen – this is key for the detailed analysis needed. Some tissue is put into paraffin blocks which is less stable. You can read more about this here.
Delays in WGS are in part due to poorly performing IT systems, which still require the use of staff filling out paper test forms to operate.
There has been a lack of attention to the infrastructure to deliver what was promised. There is a lack of human resource, so there is now a backlog.
What are we doing to address this?
Nobody wants anyone to wait over 400 days for WGS to be done. Clinicians are as frustrated as the person with the brain tumour. It is acknowledged that the NHS Genomic Medicine Service is at the vanguard of Whole Genome Sequencing – it is world leading. There is a recovery plan and the mindset is focused on sorting out the problem – that’s a good start.
At brainstrust we know that we are none of us smart as all of us. It will need collective intelligence to transform the WGS landscape so we are working with the National Cancer Research Institute, with the British Neuro-Oncology Society and also with the Tessa Jowell Brain Cancer Mission to address these challenges. There are examples where WGS can be done efficiently; the work at Cambridge, supported by the Mindaroo Foundation is one such example. We know too that patients and caregivers have a voice in this conversation but that we need to understand what’s at play. This is why we are going to be expanding on this in the next few weeks.