Genvinset® DPYD

Dihydropyrimidine dehydrogenase (DPD) deficiency is a genetic disorder that affects the metabolism of fluoropyrimidines, such as 5-fluorouracil (5-FU) and capecitabine.

These drugs are widely used in the treatment of several types of cancer, particularly gastrointestinal, colorectal, and breast cancers. However, their administration may cause severe toxicity, affecting approximately 10–40% of patients, and may include adverse events such as myelosuppression, severe diarrhea, vomiting, stomatitis, mucositis, hand-foot syndrome, or neuropathy. In some cases, toxicity may be fatal, highlighting the importance of dose adjustment before treatment initiation. For this reason, analysis of variants in the DPYD gene is recommended before treatment initiation in multiple clinical settings as part of a personalized medicine approach.

INTENDED USE

Genvinset® DPYD is a semi-automated kit for the qualitative detection of eight clinically relevant variants in the DPYD gene (OMIM: 612779): c.1905+1G>A (rs3918290; DPYD*2A), c.1679T>G (rs55886062; DPYD*13), c.1129-5923C>G (rs75017182; HapB3), c.2846A>T (rs67376798), c.1236G>A (rs56038477, HapB3), c.557A>G (rs115232898), c.868A>G (rs146356975) and c.2279C>T (rs112766203), associated with increased risk of severe or fatal toxicity linked to DPD genotyping treatment regimes, in genomic DNA extracted from whole blood or buccal swabs, using Real-Time PCR technology with specific TaqMan® probes.
This test is intended to screen patient populations who are candidates for fluoropyrimidinebased therapy and have been referred by the corresponding healthcare professional (e.g., oncologist). The test is not intended to be used in isolation for screening, monitoring, risk assessment or prognosis.

The intended user of the kit is technical personnel trained to carry out the protocol and the interpretation of results described in the instructions for use.

WORKFLOW

RESULTS

In the rest of the reactions, results are equivalent.

LIMITATIONS

• The kit detects the genotype of variants rs67376798 (NCBI dbSNP rs67376798; NM_000110.4:c.2846A>T), DPYD*2A (NCBI dbSNP rs3918290; NM_000110.4:c.1905+1G>A), DPYD*13 (NCBI dbSNP rs55886062; NM_000110.4:c.1679T>G), HapB3 (NCBI dbSNP rs75017182; NM_000110.4:c.1129-5923C>G), HapB3 (NCBI dbSNP rs56038477; NM_000110.4:c.1236G>A), rs115232898 (NCBI dbSNP rs115232898; NM_000110.4:c.557A>G), rs146356975 (NCBI dbSNP rs146356975; NM_000110.4:c.868A>G) and rs112766203 (NCBI dbSNP rs112766203; NM_000110.4:c.2279C>T) of the DPYD gene (OMIM: 612779).
• Variants at annealing primer/probe sites may result in the lack of allele definition. Other technologies could be necessary to resolve the typing. It is highly recommended for homozygous mutant samples to be confirmed by a different methodology.
• Data and result interpretation should be revised by qualified personnel.
• This product is an auxiliary tool for the detection of variants in the DPYD gene associated with a high risk of toxicity from certain pharmacological treatments. Use these results in conjunction with clinical data and results of other tests performed on the patient.