{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:12:08Z","timestamp":1760242328685},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,8,25]],"date-time":"2006-08-25T00:00:00Z","timestamp":1156464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2007,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Despite the progress of therapy, about 25% of patients with hepatoblastoma succumb to the disease. Prognostic factors, as well as improved therapies, are needed for these patients. We investigated the incidence and clinical significance of genetic and epigenetic aberrations in hepatoblastoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p><jats:italic>\u03b2<\/jats:italic>\u2010<jats:italic>catenin<\/jats:italic> mutation was analyzed by sequencing and promoter hypermethylation of the <jats:italic>RASSF1A<\/jats:italic> and <jats:italic>SFRP<\/jats:italic> genes by methylation\u2010specific PCR after bisulfate treatment of DNA samples from 39 hepatoblastomas. Association of the clinical and biological features, including sex, age of patients, stage of the disease, the histological type, and the <jats:italic>\u03b2<\/jats:italic>\u2010<jats:italic>catenin<\/jats:italic> and <jats:italic>RASSF1A<\/jats:italic> status with overall survival was evaluated using univariate and multivariate analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>\u03b2<\/jats:italic>\u2010<jats:italic>catenin<\/jats:italic> mutation and <jats:italic>RASSF1A<\/jats:italic> methylation were found in 22 (56.4%) and 15 (38.5%) of 39 hepatoblastomas, respectively, but <jats:italic>SFRP<\/jats:italic>s methylation was not found in any of them. <jats:italic>RASSF1A<\/jats:italic> and <jats:italic>SFRP<\/jats:italic>s were unmethylated in five adjacent normal liver tissues. Patients with a <jats:italic>RASSF1A<\/jats:italic> methylated tumor were older in age (\u22652 years, <jats:italic>P<\/jats:italic>\u2009=\u20090.036), at more advanced stages (<jats:italic>P<\/jats:italic>\u2009=\u20090.009), and had more frequent <jats:italic>\u03b2\u2010catenin<\/jats:italic> mutation (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) and poorer outcome (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) than those with a <jats:italic>RASSF1A<\/jats:italic> unmethylated tumor. While univariate analysis showed the prognostic significance of age, stage, the histological type, and the <jats:italic>\u03b2\u2010catenin<\/jats:italic> and <jats:italic>RASSF1A<\/jats:italic> status, multivariate analysis showed only the <jats:italic>RASSF1A<\/jats:italic> methylation status as an independent factor predicting outcome (relative risk, 10.51; 95% CI, 1.21\u2009\u223c\u200990.97; <jats:italic>P<\/jats:italic>\u2009=\u20090.033).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>RASSF1A<\/jats:italic> methylation may be a novel molecular\u2010genetic marker for treatment outcome in hepatoblastoma if confirmed by studies examining a larger number of hepatoblastomas. Pediatr Blood Cancer. Pediatr Blood Cancer 2007;49:240\u2013249. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.21031","type":"journal-article","created":{"date-parts":[[2006,8,25]],"date-time":"2006-08-25T21:34:03Z","timestamp":1156541643000},"page":"240-249","source":"Crossref","is-referenced-by-count":32,"title":["Promoter hypermethylation of the <i>RASSF1A<\/i> gene predicts the poor outcome of patients with hepatoblastoma"],"prefix":"10.1002","volume":"49","author":[{"given":"Waka","family":"Sugawara","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Haruta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumiaki","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Tsunematsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Kikuta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiko","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,8,25]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(00)00018-8"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10632"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2004.09.011"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64567-1"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2001.tb01172.x"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20227"},{"key":"e_1_2_6_8_2","first-page":"269","article-title":"Childhood hepatoblastomas frequently carry a mutated degradation targeting box of the beta\u2010catenin gene","volume":"59","author":"Koch A","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_6_9_2","first-page":"901","article-title":"Frequent deletions and mutations of the beta\u2010catenin gene are associated with overexpression of cyclin D1 and fibronectin and poorly differentiated histology in childhood hepatoblastoma","volume":"7","author":"Takayasu H","year":"2001","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1662"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-1162"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.LAB.0000059926.66359.BD"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19890901)64:5<1082::AID-CNCR2820640520>3.0.CO;2-G"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-4088"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205446"},{"key":"e_1_2_6_16_2","first-page":"2362","article-title":"Clinicopathological significance of epigenetic inactivation of RASSF1A at 3p21.3 in stage I lung adenocarcinoma","volume":"8","author":"Tomizawa Y","year":"2002","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0652"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-1331"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1053\/jpsu.2002.32886"},{"key":"e_1_2_6_20_2","unstructured":"The Japanese Society of Pathology.Committee on histological classification of childhood tumors. 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