Transforming NHS services

Whole genome sequencing (WGS) for cancer in the NHS is a big challenge.

It involves changing the way hospitals move samples from patients to laboratories. It also involves changing how laboratories and staff work.

WGS could improve pathology services, diagnosis and treatment of cancer. It can enhance, and possibly replace, current genetic testing of tumours.

Why WGS?

Cancer isn’t just one disease – it’s hundreds.

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Grade 3 breast cancer cells under the microscope

Cancer is usually diagnosed by bringing together the results of different tests. These include the results of scans, physical checks and pathological assessments. Pathological assessments involve looking at the tumour down the microscope. A pathologist looks at the size, shape and features of the cancer cells to grade their severity. Most cancers have three grades of severity. Pathologists also give a stage to the tumour. Sometimes, genetic testing of the tumour is also done.

But we know that patients with the same diagnosis and same grade may fare differently. Some will respond well to treatment, others won’t.

Whole genome sequencing is starting to tell us why. For example, WGS has recently shown there are many different types of breast cancer. Each has different changes to the DNA, the genome.

The different types may affect patients differently. Knowing which type someone has is valuable. It can help clinicians predict treatment response and give a more accurate prognosis.

What about existing genetic tests on tumours?

Some hospitals do genetic tests of tumours. There are different types of tests which look for specific changes to DNA in tumour cells.

WGS tests the whole genome at once, for all the different types of DNA changes that might be causing a cancer. WGS is sometimes cheaper than separate diagnostic tests.

This can help in diagnosis. The results can also show if a tumour might respond to a certain treatment. This could be a chemotherapy, a biological therapy or immunotherapy.

Changing Pathology Practice

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Tumour sample in FFPE

To help diagnose cancer, a sample (biopsy), of a patient’s tumour is taken. This is usually in a hospital clinic. This sample is usually very small. The sample is stored in formalin to preserve it. It is then set in wax and thinly sliced, so it can be looked at down a microscope. This process is called Formalin Fixed, Paraffin Embedded (FFPE).

We want to take DNA from these tumour samples for whole genome sequencing. ⇒ Find out more about DNA extraction and genome sequencing. But FFPE is extremely damaging to DNA. We tested it in the early stages of the 100,000 Genomes Project. Over half the samples did not pass quality controls to run WGS. Even when samples did pass quality control, we didn’t always get usable data.

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Pathology lab with samples in FFPE

To improve the quality of DNA and enable WGS, there is a different way to collect tumour samples. This is called ‘fresh frozen’ (FF). Samples are quickly processed and put in a -80°C freezer. They can be stored until the laboratory is ready to extract DNA.

But FF is much more difficult for busy NHS hospitals and clinics. Many do not currently have equipment or infrastructure to do it.

Where FF is not at all workable, we have created an ‘optimised FFPE’ process. This reduces the DNA damage. We are exploring other ways to solve the problem too. One is chilling samples where freezing is not possible. We are testing which approaches will work best.

⇒ For more information on this, please see our pages for NHS GMC staff.


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Pathology lab with frozen samples

We are working with researchers, NHS pathology services, and NHS England to introduce FF. We are extremely grateful for all the GMCs ground breaking work in this area.

Getting DNA of high enough quality for WGS, from routine clinical care, is not an issue unique to the 100,000 Genomes Project. Our work will help to inform other clinical and research studies in the NHS and around the world. Our aim is to drive up the quality of cancer DNA samples for testing in the NHS. This will serve the 100,000 Genomes Project, and improve cancer testing in the NHS overall.

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