Promoter methylation and large intragenic rearrangements of <it>DPYD </it>are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients
<p>Abstract</p> <p>Background</p> <p>Severe toxicity to 5-fluorouracil (5-FU) based chemotherapy in gastrointestinal cancer has been associated with constitutional genetic alterations of the dihydropyrimidine dehydrogenase gene (<it>DPYD</it>).</p> <...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2010-09-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/10/470 |
| _version_ | 1818117125877792768 |
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| author | Savva-Bordalo Joana Ramalho-Carvalho João Pinheiro Manuela Costa Vera L Rodrigues Ângelo Dias Paula C Veiga Isabel Machado Manuela Teixeira Manuel R Henrique Rui Jerónimo Carmen |
| author_facet | Savva-Bordalo Joana Ramalho-Carvalho João Pinheiro Manuela Costa Vera L Rodrigues Ângelo Dias Paula C Veiga Isabel Machado Manuela Teixeira Manuel R Henrique Rui Jerónimo Carmen |
| author_sort | Savva-Bordalo Joana |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Severe toxicity to 5-fluorouracil (5-FU) based chemotherapy in gastrointestinal cancer has been associated with constitutional genetic alterations of the dihydropyrimidine dehydrogenase gene (<it>DPYD</it>).</p> <p>Methods</p> <p>In this study, we evaluated <it>DPYD </it>promoter methylation through quantitative methylation-specific PCR and screened <it>DPYD </it>for large intragenic rearrangements in peripheral blood from 45 patients with gastrointestinal cancers who developed severe 5-FU toxicity. <it>DPYD </it>promoter methylation was also assessed in tumor tissue from 29 patients</p> <p>Results</p> <p>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, <it>DPYD </it>promoter methylation and large <it>DPYD </it>intragenic rearrangements were absent in all cases analyzed.</p> <p>Conclusions</p> <p>Our results indicate that <it>DPYD </it>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.</p> |
| first_indexed | 2024-12-11T04:33:27Z |
| format | Article |
| id | doaj.art-649d216d04bc4950852546e91dffbaff |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-11T04:33:27Z |
| publishDate | 2010-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-649d216d04bc4950852546e91dffbaff2022-12-22T01:20:49ZengBMCBMC Cancer1471-24072010-09-0110147010.1186/1471-2407-10-470Promoter methylation and large intragenic rearrangements of <it>DPYD </it>are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patientsSavva-Bordalo JoanaRamalho-Carvalho JoãoPinheiro ManuelaCosta Vera LRodrigues ÂngeloDias Paula CVeiga IsabelMachado ManuelaTeixeira Manuel RHenrique RuiJerónimo Carmen<p>Abstract</p> <p>Background</p> <p>Severe toxicity to 5-fluorouracil (5-FU) based chemotherapy in gastrointestinal cancer has been associated with constitutional genetic alterations of the dihydropyrimidine dehydrogenase gene (<it>DPYD</it>).</p> <p>Methods</p> <p>In this study, we evaluated <it>DPYD </it>promoter methylation through quantitative methylation-specific PCR and screened <it>DPYD </it>for large intragenic rearrangements in peripheral blood from 45 patients with gastrointestinal cancers who developed severe 5-FU toxicity. <it>DPYD </it>promoter methylation was also assessed in tumor tissue from 29 patients</p> <p>Results</p> <p>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, <it>DPYD </it>promoter methylation and large <it>DPYD </it>intragenic rearrangements were absent in all cases analyzed.</p> <p>Conclusions</p> <p>Our results indicate that <it>DPYD </it>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.</p>http://www.biomedcentral.com/1471-2407/10/470 |
| spellingShingle | Savva-Bordalo Joana Ramalho-Carvalho João Pinheiro Manuela Costa Vera L Rodrigues Ângelo Dias Paula C Veiga Isabel Machado Manuela Teixeira Manuel R Henrique Rui Jerónimo Carmen Promoter methylation and large intragenic rearrangements of <it>DPYD </it>are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients BMC Cancer |
| title | Promoter methylation and large intragenic rearrangements of <it>DPYD </it>are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients |
| title_full | Promoter methylation and large intragenic rearrangements of <it>DPYD </it>are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients |
| title_fullStr | Promoter methylation and large intragenic rearrangements of <it>DPYD </it>are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients |
| title_full_unstemmed | Promoter methylation and large intragenic rearrangements of <it>DPYD </it>are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients |
| title_short | Promoter methylation and large intragenic rearrangements of <it>DPYD </it>are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients |
| title_sort | promoter methylation and large intragenic rearrangements of it dpyd it are not implicated in severe toxicity to 5 fluorouracil based chemotherapy in gastrointestinal cancer patients |
| url | http://www.biomedcentral.com/1471-2407/10/470 |
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