A new DPYD genotyping assay for improving the safety of 5-fluorouracil therapy

作者：Sistonen Johanna^*; Smith Chingying; Fu Yung Kang; Largiader Carlo R

来源：Clinica Chimica Acta, 2012, 414: 109-111.

DOI：10.1016/j.cca.2012.08.015

• 5-Fluorouracil
• DPYD
• Genotyping
• Microarray
• Pharmacogenomics

Background: Chemotherapeutic use of 5-fluorouracil (5FU) is compromised by 10-20% of patients developing severe toxicity. Recently described genetic variation in dihydropyrimidine dehydrogenase (DPYD) has been shown to be a major predictor of 5FU toxicity. Here, we describe a new genotyping assay for routine clinical use that covers all the major DPYD risk variants. %26lt;br%26gt;Methods: Genomic regions targeting DPYD risk variants (c.1129-5923C%26gt;G, c.1679T%26gt;G/A, c.1905+1G%26gt;A, c.2846A%26gt;T) and additional markers (c.234-123G%26gt;C, c.496A%26gt;G, c.775A%26gt;G) were amplified in a multiplex PCR reaction. The subsequent steps including allele-specific primer extension, hybridization of the primers to a microarray, scanning of the array, and data analysis were automated within the INFINITI (R) Analyzer (AutoGenomics). The assay was validated by analyzing 107 blood samples obtained from patients previously re-sequenced for the DPYD. %26lt;br%26gt;Results: The genotypes obtained with the developed assay were 100% concordant with the re-sequencing. The procedure is suitable for routine clinical use since the results are obtained within one day. For heterozygous risk variant carriers (similar to 7% of Europeans), the treatment can be adjusted by 5FU dose reduction, whereas carriers of two risk alleles should be treated with an alternative therapy. %26lt;br%26gt;Conclusions: The developed assay provides a novel tool to improve the safety of commonly used 5FU-based chemotherapies.

• 出版日期2012-12-24