Interesting case of a rare variant causing a false positive DPYD result

Poster Abstract: Hazel Pearce, Clinical Scientist, NHS Wales

Abstract

Background/Aims: Fluoropyrimidines are chemotherapy drugs used to treat a wide variety of solid tumours.  While treatment is generally well-tolerated, severe, sometimes fatal, drug reactions occur in ~10-40% of patients. Loss of function variants in the gene encoding dihydropyrimidine dehydrogenase (DPYD), a key enzyme in the catabolism of fluoropyrimidines, leads to DPYD deficiency, thereby increasing the patient’s risk of toxicity. Testing for four well- characterised genetic variants using an ARMS-PCR assay has been offered in Wales since March 2020. Patients identified as having one of these variants are offered reduced dosage or alternative chemotherapeutic agents. The lab has been expanding the pharmacogenomic testing for other targets, requiring the development of a panel-based test. This included using samples previously tested for DPYD on the ARMS-PCR assay. During this process we identified that one sample previously run on the ARMS-PCR assay had shown a false positive result. A thorough investigation showed that this was caused by a rare benign DPYD variant. Subsequent testing identified additional examples of this variant causing a false positive result. In this poster we will discuss our experience of this investigation, and the lessons learnt.