We earlier highlighted the most important takeaways from the Genomics England Research Conference, including how the UK will work to build on its status as a world leader in genomics. We also wanted to put a spotlight on the exciting research that is using the data from the 100,000 Genomes Project. Here are Front Line Genomics’ research highlights from the conference:

Investigating the Role of the Microbiome in Colorectal Cancer

Incidences of Colorectal cancer are significantly higher in countries with higher meat consumption, regardless of people’s genetic background. Different diets alter the composition of the microbiome, the ecosystem of bacteria resident in the gut. Changes in the microbiome composition are linked with a number of diseases, and the importance of the microbiome in the initiation and development of colorectal cancer has been increasingly recognised in recent years.

Dr Henry Wood, University of Leeds, explained in his talk how he used the 100,000 Genomes project data to investigate the microbiome bacteria present in colorectal tumour samples. DNA was extracted from colorectal cancer tumours, and the human DNA was removed. The remaining DNA was bacterial and was referenced to microbial genomes to determine abundance and species.

It was found that primary tumours displayed a much higher abundance of bacteria compared to metastatic tumours. Metastatic tumours are formed when cancer cells from the primary tumour migrate elsewhere in the body to form a new tumour. Species distribution varied between different parts of the gut. Genetic mutations including BRAF (a proto-oncogene), and microsatellite instability (genetic hypermutability) also influenced species composition.

Dr Henry Wood, University of Leeds, explained that the results could mean that either the bacterial growth contributes directly to the cancer, or during bacterial meat metabolism carcinogens are produced as a by-product. This raises the intriguing possibility that faecal transplants or dietary changes could be viable treatments for some types of cancer.

If links can be found between certain bacterial species and cancer progression, the microbiome could become a viable cancer screening technique.

Patient Stratification

The personalised medicine model for cancer treatment aims to ensure that patients get the most effective drug treatment for their cancer subtype. Katie Ridout, University of Oxford, explained in her talk how she used data from the 100,000 Genomes project to sort chronic lymphocytic leukemia (CLL) patients into four distinct risk groups. These findings can ensure CLL patients are stratified into the best clinical trial for their disease subtype.

Both tumor and germline genetic samples were collected from 488 CLL patients. Whole genome sequencing was used to identify genetic markers that could influence disease prognosis, including mutation burden, copy number mutations and telomere length. A ‘non-negative matrix factorisation’; a type of mathematical model, was used to sort patients into four groups, depending on their disease genomic profile. Patients in the same groups shared similar prognosis predictions for their disease. Identifying patient risk can be used to inform treatment decisions.

Dr Ridout explained that the matrix model could be adapted to stratify patients of different cancers, assuming the genetic signatures of the cancer were well understood.

Reporting Secondary Findings to the Participants of the 100,000 Genomes Project

All the participants of the 100,000 Genomes Project had either a suspected rare genetic disease or cancer. In the case of patients with rare diseases, whole genome sequencing was used to provide a diagnosis and investigate the genetic basis for their disease. However, in addition to providing a diagnosis for a rare disease, sequencing can sometime throw up additional health related insights. These could include finding that a patient has variants that increase their cancer risk or predisposes them to high cholesterol.

Saskia Sanderson, University College London, presented her research investigating if and how these secondary findings should be communicated to the participants of the 100,000 Genomes Project. She hosted a workshop with the key stakeholders of this issue including; patients, healthcare professionals, policy makers and researchers, to gather thoughts and insights on the challenges and opportunities of reporting secondary findings.

Many patient participants of the 100,000 Genomes Project stated that they would like secondary findings to be returned to them, regardless of the results. However, they stated that the possibility of secondary findings was not clearly communicated to them when they joined the project, raising concerns around informed patient consent.

Clinicians say that interpreting the risk of secondary variant finding is difficult without knowing family history, and therefore best practice procedures to accurately presenting risk levels to patients must be followed.

The study emphasizes the importance of engaging patients in large scale genetic research projects.

The Economics of Delivering Sequencing on the NHS

To support the implementation of genomic sequencing services into healthcare providers, such as the NHS, the cost-effectiveness of such measures must be evaluated.

The 100,000 Genomes project contained a high number of patients with rare genetic diseases, who often go through lengthy struggles just to achieve a diagnosis. During this period, rare disease patients could require emergency care, multiple doctor’s appointments, or medications that may have no long-term benefits – all at significant costs to the health service. Therefore, although the cost of sequencing rare disease patients is significant, shortening the time it takes to get a diagnosis has the potential to recoup healthcare costs.

James Buchanan, University of Oxford, explained in his talk how the healthcare costs of rare disease patients on the 100,000 Genomes project were calculated to estimate the possible savings that earlier diagnosis using sequencing technologies could generate for the health service.

Given the NHS’ already strained budget, it’s important that genomic sequencing is implemented into the healthcare service in the most efficient way possible to ensure patient benefit without astronomical costs.

FLG’s Thoughts on Genomics England Research Conference

It was fantastic to see the innovative ways in which the 100,000 Genomes data is being used to drive research forwards. In the concluding speech it was said that we are only ‘scratching the surface on what the data can do’ – although the research is already bringing patient benefit the potential of the data is so great that many more exciting insights from the project will emerge in the coming years.

If you attended the conference, we want to hear from you! Let us know what research you thought was exciting! @FLGenomics

You can read our main takeaways from the conference here, to hear how Matt Hancock, Secretary of State for Health, and Chris Wigley, CEO of Genomics England, plan to build on the UK’s position as a world leader in the Genomics field. 

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