The Yourgene® DPYD assay allows for rapid detection of the 6 clinically relevant variants in the dihydropyrimidine dehydrogenase (DPD) enzyme.
Identification of individuals with DPD deficiency prior to commencing treatment is critical to avoid adverse reactions to chemotherapeutic agents which can be severe, and even fatal.
What is DPYD?
5-fluoracil (5-FU) is a chemotherapy agent belonging to the fluoropyrimidine family, often used to treat a range of cancers including: colorectal, head and neck, breast, pancreatic and stomach cancer. 5-FU is metabolized by the dihydropyrimidine dehydrogenase enzyme (DPD) which is encoded by the DPYD gene.
Several variants within the DPYD gene have been described that lead to decreased DPD activity, or complete loss of function. Patients with these variants are at an increased risk of severe or fatal 5-FU toxicity. Therefore, implementation of DPD deficiency screening by genotyping will allow a more accurate prediction of toxicity and chemotherapeutic response, enabling the appropriate treatment to be offered to patients.
CPIC Guidelines for DPYD
The Clinical Pharmacogenetics Consortium (CPIC) guidelines for DPYD genotyping recommend testing for the 6 clinically relevant variants outlined below:
Yourgene® DPYD assay
The method employed by the DPYD assay uses fluorescent ARMS (Amplification Refractory Mutation System) allele specific amplification technology, which detects point mutations, insertions or deletions in DNA.
Learn more about ARMS technology here.
The Yourgene® DPYD assay is available as a CE-marked in vitro diagnostic product (IVD) or Research Use Only (RUO) product.
For further information, please see our Product Menu.
Yourgene® DPYD previously known as Elucigene® DPYD.
The DPYD test is two tube assay which is easy to set up and involves minimal hands-on time. Results review and interpretation is simple with no data transfer required. The rapid 4-hour workflow allows the test to be incorporated into routine cancer care treatment pathways.
Two tube assay
Ready to use reagents
Simple data interpretation
Fast turnaround time
In line with CPIC Guidelines
DPYD Test Features
- One or two tube analysis
- Tube A: mutation detection and polyT status
- Tube B: wildtype detection
- Simple PCR set-up
- Reduced hands on time
- No post-PCR manipulation
- Compatible with ABI 3*** and SeqStudio Genetic Analysers
- Highly multiplexed 5 dye chemistry
- Rapid Analysis
- GeneMarker® and GeneMapper™ software applications
- Easy data review and analysis
- Informative single page reporting
- No data transfer required
Accuracy was determined to be 100% positive percent agreement (PPA), 100% negative percent agreement (NPA), and 100% overall agreement (OA) compared to Sanger sequencing Accuracy of the DPYD assay was assessed by evaluating 103 samples representing a wide variety of gene variants from four separate sources.
Repeatability results showed 100% PPA, 100% NPA, and 100% OA. This data provides evidence that the DPYD assay produces consistently repeatable results.
Reproducibility results showed 100% PPA, 100% NPA, and 100% OA. This data provides evidence that the DPYD assay produces consistently reproducible results.
Patient and Healthcare Provider views on DPD deficiency screening
Dr Gabriel Brooks (GB) is a Medical Oncologist specialising in treating gastrointestinal cancers at Darmouth-Hitchcock Medical Centre. He has a specialist interest in DPD deficiency and cancer care delivery research.
Holly Ellis (HE) and Hannah Stevens (HS) are both scientists working in Genomics in the NHS. They have both been involved in establishing and running a DPYD testing service at the hospital for routine testing of patients undertaking chemotherapy. Holly is also known on social media as ‘The Scouse Scientist’. In this role she aims to break stereotypes in science, as well as educate and inform the general public on issues such as the use of genomics in precision medicine.
"It is clear that testing has a key role to play in managing a successful response to the COVID-19 pandemic. Alongside continuing to support initiatives that foster a robust viral testing and tracing programme, Governments across the world should look to examples of where other testing, such as DPYD screening, is being used innovatively to reduce the burden on resources of critical importance during the pandemic. "
View the full Your Comment articles below
The role of DPYD testing in managing a successful response to the COVID-19 pandemic - 5 November 2020
The role of DPYD testing in managing a successful response to the COVID-19 pandemic – 5 November 2020
Since the beginning of the global COVID-19 outbreak, the diagnostic and research community has undertaken an unprecedented effort to understand how best to manage, eradicate and prevent the disease. Two key pillars in the fight against the pandemic are establishing a robust testing strategy and implementing procedures and processes to reduce the burden on healthcare systems.
Independent SAGE recently published a document containing core recommendations for how best to optimize and develop the current testing environment (1). It is clear that a wider reaching, more efficient testing strategy is desperately needed – in the UK Baroness Harding (head of NHS Test and Trace) recently briefed the science and technology committee that the number of individuals looking to book a test was three to four times the capacity of the service (2). Outside of the centralised testing systems employed by most Governments across the world, many businesses keen to bring staff back into the workplace have turned to private health companies to meet demand. Other sectors, including universities and independent schools, have also contributed to demand for private testing being thirty times higher than that seen in the summer (3). Facilities have responded in kind, with some creating ‘pop up’ facilities to facilitate the collecting and processing of extra samples (3). Manufacturers of testing kits have also responded by focusing efforts on maximising the ease and efficiency of testing. One area of innovation has been optimising saliva testing in order to move away from the need for nasopharyngeal swabs, which is labour intensive and usually requires close contact with a healthcare professional.
Despite the collective effort of both the public and private healthcare sectors to increase capacity and develop the testing pathway, diagnosing and identifying cases remains only one of the pillars needed to protect communities and manage the pandemic.
At the onset of the pandemic countries across the world put in place national initiatives to increase the number of available hospital beds and associated staffing resource. Leishenshan Hospital in Wuhan was one of the hospitals built by China in order to handle the large number of COVID-19 patients. The hospital was built in a record time of just 2 weeks, whilst in the UK 7 critical care hospitals were opened in the space of just over a month.
Alongside such efforts to expand capacity, healthcare systems have worked to reduce the burden on resources – in particular the demand for intensive care unit (ICU) beds. In many countries the public were asked to stay at home except where absolutely necessary, such as to buy food or care for a vulnerable family member. This not only reduced the spread of COVID-19, but also reduced the number of accidents that are associated with travel. In the Tarragona province of Spain the number of traffic accidents fell by almost 75% (4). Difficult decisions were made around prioritising ICU beds and treatment for those critically ill patients who were most likely to benefit from such intervention (5). However, arguably the intervention with the largest impact was many hospitals making the decision to downscale all out-patient clinics and non-urgent interventions and surgeries. Policies were clear, however, that all cancer treatments and other clinically urgent care should continue unaffected (6).
This raises the question as to whether there are available strategies that could be implemented to reduce the need for intensive care escalation among patients undergoing cancer treatments or other urgent interventions. Fluorouracil (5-FU) and Capecitabine, a prodrug of 5-FU, are fluoropyrimidine chemotherapy agents used in the treatment of cancer. These drugs form a key component of the chemotherapy regime for colorectal, breast, heapato-pancreato-biliary and many other cancers. These drugs are catabolised by the dihydropyrimadine deyhydrogenase (DPD) enzyme, itself encoded by the DPYD gene. Approximately 3–5% of the European population have a partial DPD enzyme deficiency due to a mutation in the gene (7), and complete enzyme deficiency has also been described. In the US it is reported that up to 8% of the general population have at least a partial deficiency (8). Individuals with a complete deficiency are at risk of life threatening or even fatal chemotherapy toxicity when given 5-FU or Capecitabine. Those with a partial deficiency usually experience gastrointestinal adverse reactions such as prolonged vomiting, as well as haematological effects including a decreased white blood cell count when given therapy at the standard dose. The latter puts patients at risk of serious infection, and a fever is often also reported in those with a partial deficiency. Some studies have shown that almost 25% of patients who are given fluoropyrimidine chemotherapy as a first-line drug experience severe toxicity (9). DPYD testing allows for those with a partial or complete deficiency to be identified, and either a modified dose or alternative therapy given to prevent such adverse reactions. In addition to the clear clinical benefit for the patient, a recent study reported that the average cost of an ICU admission following DPYD toxicity was almost €47,000 per person, and as such that pre-emptive DPYD screening of all patients is a cost-effective strategy (9). Many countries are beginning to recognise the clinical and economic benefit of universal pre-emptive DPYD genotyping. Wales is the first nation in the UK to offer the DPYD test to all patients, with over 400 samples already taken and 6% of patients returning a positive result. All Wales Medical Genomics Service (AWMGS) commenced a pilot phase earlier this year using the Elucigene DPYD assay, which then led to the launch of the nation-wide service (10). Similarly the German Federal Joint Committee, G-BA, the national reimbursement authority in Germany, recently approved reimbursement for DPYD testing across the country. Many countries could benefit from adopting similar approaches, especially in the current climate of extra pressure on ICU resources.
It is clear that testing has a key role to play in managing a successful response to the COVID-19 pandemic. Alongside continuing to support initiatives that foster a robust viral testing and tracing programme, Governments across the world should look to examples of where other testing, such as DPYD screening, is being used innovatively to reduce the burden on resources of critical importance during the pandemic.
Click here to find out how Yourgene Health can support your organisation in delivering COVID testing. You can also find out how about our range of genotyping tests, including our CE-marked DPYD assay.
1. Independent SAGE: The complexities of testing for COVID-19: the why, the who and the how https://www.independentsage.org/wp-content/uploads/2020/09/Indie-SAGE-testing-document-Final-110920-12.05.pdf
2. Coronavirus: Test demand ‘significantly outstripping’ capacity https://www.bbc.co.uk/news/uk-54194302
3. Private groups race to meet Covid testing demand from UK companies https://www.ft.com/content/17c5a06e-7987-415f-ad60-78102535a12f
4. COVID-19 lockdown and reduction of traffic accidents in Tarragona province, Spain https://www.sciencedirect.com/science/article/pii/S2590198220301299
5. Prioritisation of ICU treatments for critically ill patients in a COVID-19 pandemic with scarce resources https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230138/
6. Covid-19: all non-urgent elective surgery is suspended for at least three months in England https://www.bmj.com/content/368/bmj.m1106
7. DPYD Testing – Manchester University https://mft.nhs.uk/dpyd/
8. Dihydropyrimidine dehydrogenase deficiency https://rarediseases.info.nih.gov/diseases/19/dihydropyrimidine-dehydrogenase-deficiency
9. Cost Implications of Reactive Versus Prospective Testing for Dihydropyrimidine Dehydrogenase Deficiency in Patients With Colorectal Cancer: A Single-Institution Experience https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168732/
10. Elucigene DPYD tests to be used routinely in Wales https://www.yourgene-health.com/about/press-releases/20-news/1702-12-october-2020-elucigene-dpyd-tests-to-be-used-routinely-in-wales
Video and testimonial from Louise Brown, founder of 5FU Alliance.
Interpretation of DPYD testing results by Holly Ellis, The Scouse Scientist.
DPYD Guidelines and Press Releases
DPYD screening recommended in Spain
Contract Award for the supply of DPYD testing kits to NHS Wales
DPYD screening recommended in Belgium
DPYD kits recommended by NHS England
DPYD tests to be used routinely in Wales
DPD reimbursement in Germany
NHS England – Clinical Commissioning Urgent Policy Statement
Clinical Pharmacogenetics Consortium (CPIC) guidelines for DPYD genotyping
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