The assay covers DPYD mutation IVS14+1 G-A.
The pyrimidine analogue 5-fluorouracil (5-FU) is widely used for chemotherapy of solid tumors, such as colorectal, breast, head/neck, ovarian and skin cancer. More than 80% of administered 5-FU is rapidly detoxified in the liver via a multistep metabolic pathway, involving dihydropyrimidine dehydrogenase (DPD) as the initial and rate-limiting enzyme. Individuals with low DPD activity (about 3-5% of patients) cannot effectively inactivate 5-FU, and will develop severe to lethal haematological, gastrointestinal or neurological toxicities. In the majority of cases, a G to A mutation in the splicing recognition sequence of intron 14 (IVS14+1 G-A) of the DPD-encoding gene DPYD was shown to be responsible. The mutant allele, designated DPYD*2A, produces a nonfunctional enzyme due to skipping of exon 14. It was recommended that screening for IVS14+1 G-A should be routinely carried out prior to start of 5-FU therapy, and that heterozygotes should receive limited dose of 5-FU only, while homozygotes, who are at high risk to develop severe complications, should be treated with alternative therapeutic drugs.