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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2010

Autores

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

Revista

Título: BMC Cancer

Vol. 10

Página Final: 470

ISSN: 1471-2407

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 18 Citações

Scopus - 20 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 7