{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:36:30Z","timestamp":1792146990613,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,7,27]],"date-time":"2012-07-27T00:00:00Z","timestamp":1343347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2012,9]]},"abstract":"Summary<\/jats:title>The TP<\/jats:styled-content>53 (p53) pathway can be inhibited by TP<\/jats:styled-content>53<\/jats:italic> mutation or deletion or by MDM<\/jats:styled-content>2 overexpression. Both occur in B<\/jats:styled-content>urkitt lymphoma (BL<\/jats:styled-content>), but many cases lack either abnormality. Expression patterns of the TP<\/jats:styled-content>53 inhibitor MDM<\/jats:styled-content>4 have not been reported in BL<\/jats:styled-content>, and increased MDM<\/jats:styled-content>4 could deregulate the TP<\/jats:styled-content>53 pathway in cases without TP<\/jats:styled-content>53<\/jats:italic> or MDM<\/jats:styled-content>2 abnormalities. We investigated TP<\/jats:styled-content>53 pathway disruption in paediatric BL<\/jats:styled-content> patient samples (n<\/jats:italic>\u00a0=\u00a030) by studying MDM<\/jats:styled-content>4, MDM<\/jats:styled-content>2, and CDKN<\/jats:styled-content>1A<\/jats:styled-content> (p21) protein and mRNA<\/jats:styled-content> expression; TP<\/jats:styled-content>53<\/jats:italic> mutations; TP<\/jats:styled-content>53 protein expression; and gene copy number abnormalities. MDM<\/jats:styled-content>4 protein was expressed in 30\/30 tumours, and MDM<\/jats:styled-content>2 protein was weakly expressed in 7\/30 (23%). All cases were negative for CDKN<\/jats:styled-content>1A<\/jats:styled-content> protein, and CDKN<\/jats:styled-content>1A<\/jats:styled-content><\/jats:italic> mRNA<\/jats:styled-content> levels were decreased. TP<\/jats:styled-content>53<\/jats:italic> mutations were detected in 5\/28 (18%) cases and confirmed by sequencing. TP<\/jats:styled-content>53 protein was expressed in 15\/30 (50%) cases, including 7\/8 with TP<\/jats:styled-content>53<\/jats:italic> genetic alterations. MDM<\/jats:styled-content>2 protein and mRNA<\/jats:styled-content> expression levels did not correlate with lack of TP<\/jats:styled-content>53<\/jats:italic> genetic changes or TP<\/jats:styled-content>53 protein expression; however, there was an inverse relationship between detectable TP<\/jats:styled-content>53 protein expression and MDM<\/jats:styled-content>4<\/jats:italic> copy number gains and mRNA<\/jats:styled-content> expression. The TP<\/jats:styled-content>53 pathway is deregulated in paediatric BL<\/jats:styled-content> cases, and increased MDM<\/jats:styled-content>4 expression may be the primary mechanism in some cases.<\/jats:p>","DOI":"10.1111\/j.1365-2141.2012.09243.x","type":"journal-article","created":{"date-parts":[[2012,7,27]],"date-time":"2012-07-27T23:37:54Z","timestamp":1343432274000},"page":"763-771","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["TP<\/scp>53 pathway analysis in paediatric B<\/scp>urkitt lymphoma reveals increased MDM<\/scp>4<\/i> expression as the only TP<\/scp>53 pathway abnormality detected in a subset of cases"],"prefix":"10.1111","volume":"158","author":[{"given":"Vasiliki","family":"Leventaki","sequence":"first","affiliation":[{"name":"Department of Pathology University of Utah Health Sciences Center Salt Lake City UT 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