{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T05:02:00Z","timestamp":1696914120421},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,5,4]],"date-time":"2004-05-04T00:00:00Z","timestamp":1083628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"German Research Council","award":["Pi191\/9-1"],"award-info":[{"award-number":["Pi191\/9-1"]}]},{"name":"Bennigsen-Foerder Foundation"},{"name":"Sender Hoffman Memorial Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2004,9,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chromosomal region 11p15.5 shows frequent maternal allelic loss in embryonal tumors, including rhabdomyosarcoma (RMS), Wilms' tumor (WT) and hepatoblastoma (HB), consistent with the presence of at least one tumor suppressor gene in this region, which should be paternally imprinted, <jats:italic>i.e.<\/jats:italic>, expressed from the maternal allele only. The <jats:italic>BWR1A<\/jats:italic> gene encodes a polyspecific transmembrane transporter and is located on 11p15.5. It is highly expressed in liver, paternally imprinted and was found to be mutated in an RMS cell line, making it a plausible tumor suppressor gene for HB. We therefore screened 62 HBs, 3 HB cell lines and 1 pediatric hepatocellular carcinoma for <jats:italic>BWR1A<\/jats:italic> mutations using single\u2010strand conformation polymorphism analysis. Allelic loss on 11p15.5 was assessed by PCR\u2010based microsatellite analysis in 56 of the cases for which constitutional DNA was available. <jats:italic>BWR1A<\/jats:italic> mRNA expression was determined in 14 HBs by differential RT\u2010PCR of matched cDNA samples from tumor and normal liver. Western blot analysis was performed on 4 tumors and matching normal liver tissue. Except for sequence polymorphisms (in exons 2, 3 and 10 as well as in introns 6 and 7), no mutations were found. Thirteen HBs (23%) had allelic loss on 11p15.5; this included <jats:italic>BWR1A<\/jats:italic> in 12 but it was telomeric to <jats:italic>BWR1A<\/jats:italic> in 1. Expression of <jats:italic>BWR1A<\/jats:italic> mRNA was reduced in 11 out of 14 cases by 19\u201492%, independent from allelic loss of 11p15.5. By Western blot analysis, all 4 tumors and matching liver samples displayed a 48\u201351 kd band corresponding to BWR1A. These results make it unlikely that <jats:italic>BWR1A<\/jats:italic> is the target of the allelic deletions in HB. However, similar to the putative 11p15.5 tumor suppressor <jats:italic>H19<\/jats:italic>, <jats:italic>BWR1A<\/jats:italic> appears to be reduced in expression. Reduced expression in the absence of mutations may contribute to HB development; however, to understand the significance of this finding will require further studies on the function of <jats:italic>BWR1A<\/jats:italic>, specifically its role in liver development. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.20280","type":"journal-article","created":{"date-parts":[[2004,5,4]],"date-time":"2004-05-04T18:01:04Z","timestamp":1083693664000},"page":"627-632","source":"Crossref","is-referenced-by-count":18,"title":["Allelic loss but absence of mutations in the polyspecific transporter gene <i>BWR1A<\/i> on 11p15.5 in hepatoblastoma"],"prefix":"10.1002","volume":"111","author":[{"given":"Steffen","family":"Albrecht","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farzad","family":"Houshdaran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arend","family":"Koch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"G\u00e4rtner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Prawitt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernhard 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