{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T16:38:47Z","timestamp":1793983127883,"version":"4.8.0"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,12,19]],"date-time":"2003-12-19T00:00:00Z","timestamp":1071792000000},"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":[[2004,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>There is evidence that 8q amplification is associated with poor prognosis in hepatoblastoma. A previous comparative genomic hybridization analysis identified a critical region in chromosomal bands 8q11.2\u2013q13. Using restriction landmark genomic scanning in combination with a virtual genome scan, we showed that this region is delineated by sequences within contig NT_008183 of chromosomal subbands 8q11.22\u2013q11.23. A real\u2010time PCR\u2013based genomic copy number assay of 20 hepatoblastomas revealed gain or amplification in this critical chromosomal region in eight tumors. The expression of four genes and expressed sequence tags (ESTs) within this newly defined region was assayed by real\u2010time reverse transcriptase polymerase chain reaction (RT\u2010PCR) in four tumors with and six tumors without gain or amplification. The <jats:italic>PLAG1<\/jats:italic> oncogene was found to be highly expressed in all but one tumor compared to normal liver tissue. Furthermore, quantitative RT\u2010PCR revealed that the expression level of the developmentally regulated transcription factor <jats:italic>PLAG1<\/jats:italic> was 3\u201312 times greater in hepatoblastoma tumors and cell lines compared to age\u2010matched normal liver and comparable to the expression in fetal liver tissue. <jats:italic>PLAG1<\/jats:italic> has been shown be a transcriptional activator of <jats:italic>IGF<\/jats:italic>2 in other tumor types. Using luciferase reporter assays, we demonstrated that <jats:italic>PLAG1<\/jats:italic> transactivates transcription from the embryonic <jats:italic>IGF2<\/jats:italic> promoter P3, also in hepatoblastoma cell lines. Thus, our results provide evidence that <jats:italic>PLAG1<\/jats:italic> overexpression may be responsible for the frequently observed up\u2010regulation of <jats:italic>IGF2<\/jats:italic> in hepatoblastoma and therefore may be implicated in the molecular pathogenesis of this childhood neoplasia. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.10307","type":"journal-article","created":{"date-parts":[[2003,12,23]],"date-time":"2003-12-23T10:01:47Z","timestamp":1072173707000},"page":"126-137","source":"Crossref","is-referenced-by-count":105,"title":["Amplification and overexpression of the <i>IGF2<\/i> regulator <i>PLAG1<\/i> in hepatoblastoma"],"prefix":"10.1002","volume":"39","author":[{"given":"Andrea","family":"Zatkova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Marie","family":"Rouillard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara J.","family":"Lamb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rork","family":"Kuick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Eckart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietrich","family":"von 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