{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:35:03Z","timestamp":1768696503365,"version":"3.49.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2010,9,1]],"date-time":"2010-09-01T00:00:00Z","timestamp":1283299200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats: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 (<jats:italic>DPYD<\/jats:italic>).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>In this study, we evaluated <jats:italic>DPYD<\/jats:italic> promoter methylation through quantitative methylation-specific PCR and screened <jats:italic>DPYD<\/jats:italic> for large intragenic rearrangements in peripheral blood from 45 patients with gastrointestinal cancers who developed severe 5-FU toxicity. <jats:italic>DPYD<\/jats:italic> promoter methylation was also assessed in tumor tissue from 29 patients<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Two cases with the IVS14+1G &gt; A exon 14 skipping mutation (c.1905+1G &gt; A), and one case carrying the 1845 G &gt; T missense mutation (c.1845G &gt; T) in the DPYD gene were identified. However, <jats:italic>DPYD<\/jats:italic> promoter methylation and large <jats:italic>DPYD<\/jats:italic> intragenic rearrangements were absent in all cases analyzed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our results indicate that <jats:italic>DPYD<\/jats:italic> 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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2407-10-470","type":"journal-article","created":{"date-parts":[[2010,9,1]],"date-time":"2010-09-01T18:15:22Z","timestamp":1283364922000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Promoter methylation and large intragenic rearrangements of DPYD are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients"],"prefix":"10.1186","volume":"10","author":[{"given":"Joana","family":"Savva-Bordalo","sequence":"first","affiliation":[]},{"given":"Jo\u00e3o","family":"Ramalho-Carvalho","sequence":"additional","affiliation":[]},{"given":"Manuela","family":"Pinheiro","sequence":"additional","affiliation":[]},{"given":"Vera L","family":"Costa","sequence":"additional","affiliation":[]},{"given":"\u00c2ngelo","family":"Rodrigues","sequence":"additional","affiliation":[]},{"given":"Paula C","family":"Dias","sequence":"additional","affiliation":[]},{"given":"Isabel","family":"Veiga","sequence":"additional","affiliation":[]},{"given":"Manuela","family":"Machado","sequence":"additional","affiliation":[]},{"given":"Manuel R","family":"Teixeira","sequence":"additional","affiliation":[]},{"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[]},{"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2010,9,1]]},"reference":[{"key":"2269_CR1","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/nrc1074","volume":"3","author":"D Longley","year":"2003","unstructured":"Longley D, Harkin DP, Johnston P: 5-fluorouracil: mechanisms of action and clinical strategies. 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