Promoter methylation and large intragenic rearrangements of DPYD are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients

作者：Savva Bordalo Joana; Ramalho Carvalho Joao; Pinheiro Manuela; Costa Vera L; Rodrigues Angelo; Dias Paula C; Veiga Isabel; Machado Manuela; Teixeira Manuel R; Henrique Rui; Jeronimo Carmen^*

来源：BMC Cancer, 2010, 10: 470.

DOI：10.1186/1471-2407-10-470

Background: Severe toxicity to 5-fluorouracil (5-FU) based chemotherapy in gastrointestinal cancer has been associated with constitutional genetic alterations of the dihydropyrimidine dehydrogenase gene (DPYD).
Methods: In this study, we evaluated DPYD promoter methylation through quantitative methylation-specific PCR and screened DPYD for large intragenic rearrangements in peripheral blood from 45 patients with gastrointestinal cancers who developed severe 5-FU toxicity. DPYD promoter methylation was also assessed in tumor tissue from 29 patients
Results: Two cases with the IVS14+1G > A exon 14 skipping mutation (c. 1905+1G > A), and one case carrying the 1845 G > T missense mutation (c. 1845G > T) in the DPYD gene were identified. However, DPYD promoter methylation and large DPYD intragenic rearrangements were absent in all cases analyzed.
Conclusions: Our results indicate that DPYD promoter methylation and large intragenic rearrangements do not contribute significantly to the development of 5-FU severe toxicity in gastrointestinal cancer patients, supporting the need for additional studies on the mechanisms underlying genetic susceptibility to severe 5-FU toxicity.

• 出版日期2010-9-1