Genomics

The Genomics team work with NHS laboratories (labs) to bring genomic testing data into the National Disease Registration Service (NDRS).

Genomic testing is any test carried out on genetic material – usually deoxyribonucleic acid (DNA), but sometimes ribonucleic acid (RNA). Sometimes it is easier to obtain the same information by testing a specific protein rather than the genetic material itself.

Genes are made from DNA, which is located in the nucleus of a cell. A gene is essentially a ‘recipe’ to make a specific protein. When a gene is switched on, an RNA copy of the gene is made, and exits the nucleus into the cytoplasm. The RNA acts as the template to make the protein.

The image below shows the genes (made from DNA) in the nucleus of the cell. Proteins are made in a different compartment of the cell: the cytoplasm.

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The image below shows the flow of information within a cell, from DNA to RNA to protein. RNA acts as a messenger; it brings instructions from the gene (in the nucleus) to the protein synthesis machinery (in the cytoplasm).

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All cancer cells contain errors in their DNA. These DNA errors drive the abnormal behaviour of the cancer cell. Genomic testing enables us to understand which genes are damaged, and how. It gives us useful information about the biology of the tumour, how it is likely to behave, and what its weak spots are. If we carry out a genetic test directly on a tumour, this is called a somatic test.

‘Somatic’ means that the DNA errors have occurred during a person’s lifetime, and only appear in the cancer cells themselves – i.e. they are not inherited from a parent and cannot be passed on to children.

There are several reasons why NHS labs perform genomic tests on tumours (i.e. somatic tests):

1. Diagnosis. Sometimes a genomic test can tell us exactly what sort of cancer a person has. For example, an abnormal fusion between two genes, BCR and ABL, is involved in almost all cases of chronic myeloid leukaemia (CML).
2. Monitoring of treatment. In the example above, we can monitor levels of the abnormal BCR-ABL fusion in a leukaemia patient’s blood. This can tell us how well their treatment is working.
3. Prognosis. Some genomic tests can tell us how aggressive a cancer is likely to be. For example, some children with acute lymphoblastic leukaemia have an abnormal RUNX1 gene in their leukaemia cells. We know that a leukaemia where RUNX1 is fused to another gene called ETV6 is less aggressive than a leukaemia in which there are too many copies of the RUNX1 gene. This might guide medical decisions as to how intensive chemotherapy treatment should be.
4. Suitability for a targeted treatment. In some cancers, if we know which key gene is damaged (and therefore which protein is abnormal), we can prescribe a drug that directly targets the abnormal protein. For example, about 11-12% of non-small cell lung cancers (NSCLC) have an error in their EGFR gene. Patients whose tumours have EGFR errors can be treated with a type of targeted drug called a ‘tyrosine kinase inhibitor (TKI)’. These targeted treatments generally have fewer side effects than chemotherapy and are more effective.

Most of the genomic data we currently collect relates to the last category – i.e. assessment of a tumour for suitability for targeted treatment. It is important to monitor who is receiving these tests and that people are getting the right drugs. In future years, we will collect and process more genomic data relating to diagnosis, monitoring and prognosis.

Some people have inherited a predisposition to developing cancer. This means that the DNA error is present in every cell in their body and can be passed on to children.

A ‘germline’ genetic test means that we are looking for a DNA variant that is part of somebody’s inherited genetic makeup. This sort of test is usually done on blood, rather than a tumour.

It is important to identify people with a genetic predisposition to cancer, so that they can be offered regular screening or, in some cases, medication or surgery to reduce their risk of cancer. Other family members might want to have a genetic test to see if they have also inherited the gene with the error. They will be offered genetic counselling so that they can talk through their options for genetic testing and screening.

NHS labs test a variety of cancer predisposition genes. Which genes are tested depends upon what types of cancer have occurred in a particular family. For example, in a family where there has been a lot of breast and ovarian cancer, a lab might look for harmful variants in the BRCA1 and BRCA2 genes.

NDRS collects data on all these genetic tests and records the exact details of any harmful (or potentially harmful) genetic variants that have been found by the NHS labs carrying out genomic testing.

By matching up the genetic variants to information in the cancer registry, we can understand more about which genetic variants are the most harmful, and what tumour characteristics are associated with each genetic variant.

We work closely with NHS genetics clinics and labs to ensure they can obtain useful insights from this work. This helps to ensure that all the NHS genetics services have access to the best national information, rather than just information from their own lab. It means that the best possible evidence is used when personalising care for every cancer-prone family in the country.

The image below summarises the above descriptions of how genomic testing can be either somatic or germline and is for illustrative purposes only:

One of the most important things we do within the genomics team is to support NHS genetic counselling clinics for people who might have inherited a tendency to develop cancer.

Most cancer is not inherited. However, in some families, similar cancers occur in several close relatives, perhaps at an unusually young age. Families like this are offered genetic counselling in an NHS clinic, where their cancer risk is assessed, and family members can be offered screening and / or genetic testing, where appropriate. In some families, an inherited genetic variant explains the cancers in the family.

Find out how NDRS supports genetic counselling services in the NHS