{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T05:30:34Z","timestamp":1697520634593},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,9,21]],"date-time":"2004-09-21T00:00:00Z","timestamp":1095724800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The fragile histidine triad (<jats:italic>FHIT<\/jats:italic>) gene, a potential tumor\u2010suppressor gene, is frequently inactivated in multiple human cancers. However, the <jats:italic>FHIT<\/jats:italic> gene remains largely unexplored in Burkitt's lymphoma (BL). Hence, we assessed whether loss of <jats:italic>FHIT<\/jats:italic> expression occurs in BL, and, if so, what is the mechanism of such loss. Lack of protein expression was observed in 50% of BL cell lines. Methylation\u2010specific polymerase chain reaction (MSP) showed that 45% of BL cell lines carried aberrantly methylated <jats:italic>FHIT<\/jats:italic> alleles. Sequencing of bisulfite\u2010treated DNA confirmed these data and indicated a very high density of methylation in all methylated alleles. Real\u2010time, quantitative reverse\u2010transcription PCR analysis indicated that attenuation of full\u2010length <jats:italic>FHIT<\/jats:italic> transcription was correlated with methylation. Sequencing of transcripts illustrated that aberrant transcription resulting in loss of <jats:italic>FHIT<\/jats:italic> exons occurred more commonly in BL containing unmethylated <jats:italic>FHIT genes<\/jats:italic>. However, such transcripts often coexisted with full\u2010length <jats:italic>FHIT<\/jats:italic> transcripts. Not surprisingly, therefore, loss of FHIT protein in BL correlated with CpG island methylation, rather than with aberrant transcription. <jats:italic>FHIT<\/jats:italic> methylation also was detected in 31% (16 of 51) of the primary BLs examined, including 2 samples whose derived cell lines also manifested <jats:italic>FHIT<\/jats:italic> hypermethylation. Aberrant methylation can thus occur in vivo. In summary, this report provides evidence that epigenetic modification frequently results in loss of <jats:italic>FHIT<\/jats:italic> expression in BL. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20099","type":"journal-article","created":{"date-parts":[[2004,9,21]],"date-time":"2004-09-21T21:00:26Z","timestamp":1095800426000},"page":"321-329","source":"Crossref","is-referenced-by-count":7,"title":["Frequent silencing of fragile histidine triad gene (<i>FHIT<\/i>) in Burkitt's lymphoma is associated with aberrant hypermethylation"],"prefix":"10.1002","volume":"41","author":[{"given":"Azhar","family":"Hussain","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina 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