{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T14:26:47Z","timestamp":1744640807114},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2003,10,24]],"date-time":"2003-10-24T00:00:00Z","timestamp":1066953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Med. Pediatr. Oncol."],"published-print":{"date-parts":[[2003,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hypermethylation of CpG islands in the promoter region of death\u2010associated protein kinase (DAP\u2010kinase) coupled with the loss of \u03b3\u2010interferon\u2010induced apoptosis have been reported in B\u2010cell malignancies suggesting a role in pathogenesis or prognosis. Along with B\u2010cell malignancies, pediatric lymphomas also include T\u2010cell non\u2010Hodgkin lymphoma (NHL), anaplastic large cell lymphoma, and Hodgkin disease, each with unique prognoses. The purpose of this study was to elucidate epigenetic changes in the DAP\u2010kinase promoter region of pediatric cases to determine associations with aberrant hypermethylation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedures<\/jats:title><jats:p>Thirty\u2010nine cases of different lymphoid pathology [10 Burkitt lymphoma, 1 B\u2010cell NHL; 7 T\u2010cell lymphoblastic lymphoma; 4 anaplastic large cell lymphoma (LCL); 2 B\u2010cell LCL; 14 nodular sclerosing Hodgkin disease (NSHD); and 1 B\u2010cell acute lymphoblastic leukemia (ALL)] had methylation\u2010specific polymerase chain reaction performed on bisulfite\u2010treated DNA, which distinguishes the methylation status of the promoter region, and DAP\u2010kinase mRNA expression assays performed on available specimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In normal lymphocytes, the CpG islands in the promoter region were unmethylated, as were the T\u2010cell lymphoblastic lymphoma and anaplastic LCL. In contrast, 100% of the Burkitt lymphoma (10\/10) and B\u2010cell ALL (1\/1) were hypermethylated. Of the specimens with mRNA available, 7\/8 Burkitt lymphoma had no DAP\u2010kinase mRNA expression compared to normal expression in 3\/3 and 4\/4 T\u2010cell lymphoblastic lymphoma and NSHD, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In these pediatric lymphoid tumors, hypermethylation of the DAP\u2010kinase promoter region with associated loss of DAP\u2010kinase gene expression was associated with B\u2010cell malignancies and thus may be important in the development and\/or provide a prognostic tool in B\u2010 cell lymphomas. Med Pediatr Oncol 2003;41:527\u2013531. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mpo.10326","type":"journal-article","created":{"date-parts":[[2003,10,29]],"date-time":"2003-10-29T11:00:29Z","timestamp":1067425229000},"page":"527-531","source":"Crossref","is-referenced-by-count":9,"title":["Epigenetic changes in the DAP\u2010kinase CpG island in pediatric lymphoma"],"prefix":"10.1002","volume":"41","author":[{"given":"Bruce","family":"Shiramizu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Mick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,10,24]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00411112"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197812282992606"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.bmb.a011579"},{"issue":"5","key":"e_1_2_1_5_2","doi-asserted-by":"crossref","first-page":"S115","DOI":"10.1093\/annonc\/9.suppl_5.S115","article-title":"Pediatric Hodgkin's disease: Treatment in the late 1990s","volume":"9","author":"Schellong G","year":"1998","journal-title":"Ann Oncol"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/1040-8428(92)90017-K"},{"key":"e_1_2_1_7_2","first-page":"265","article-title":"Prognostic features and obstacles to cure of childhood non\u2010Hodgkin's lymphoma","volume":"4","author":"Murphy SB","year":"1977","journal-title":"Semin Oncol"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/7.suppl_4.S73"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0268-960X(91)90040-J"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201172"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205195"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/36599"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.12.4347"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.5.998"},{"key":"e_1_2_1_15_2","first-page":"332","article-title":"Classification, staging, and end results of treatment of childhood non\u2010Hodgkin's lymphomas: Dissimilarities from lymphomas in adults","author":"Murphy SB","year":"1980","journal-title":"Semin Oncol"},{"key":"e_1_2_1_16_2","doi-asserted-by":"crossref","unstructured":"HarrisNL JaffeES DieboldJ.2000.The World Health Organization classification of neoplastic diseases of the haematopoietic and lymphoid tissues: Report of the Clinical Advisory Committee Meeting Airlie House Virginia November 1997. 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