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

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Savva Bordalo, J (Author) Other; Ramalho Carvalho, J (Author) Other; Pinheiro, M (Author) Other; Costa, VL (Author) Other; Rodrigues, A (Author) Other; Dias, PC (Author) Other; Veiga, I (Author) Other; Machado, M (Author) Other; Manuel R Teixeira (Author) ICBAS; henrique, rmf (Author) ICBAS; Carmen Jeronimo (Author) ICBAS

Journal

Title: BMC Cancer

Vol. 10

Final page: 470

ISSN: 1471-2407

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 18 Citations

Scopus - 20 Citations

Other information

Authenticus ID: P-003-34Z

DOI: 10.1186/1471-2407-10-470

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7