{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:47:17Z","timestamp":1791298037230,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,3,26]],"date-time":"2004-03-26T00:00:00Z","timestamp":1080259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["CA48031"],"award-info":[{"award-number":["CA48031"]}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"crossref","award":["DAMD 17-99-1-9504"],"award-info":[{"award-number":["DAMD 17-99-1-9504"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100003135","name":"Minnesota Ovarian Cancer Alliance","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100003135","id-type":"DOI","asserted-by":"crossref"}]},{"name":"DFG","award":["Kl-1134\/2-2"],"award-info":[{"award-number":["Kl-1134\/2-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2004,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The <jats:italic>Parkin<\/jats:italic> gene is an extremely large gene (1.5 Mb) within the highly unstable FRA6E common fragile site (CFS) region, which is frequently altered in ovarian, breast, and hepatocellular carcinomas. Because <jats:italic>Parkin<\/jats:italic>\/FRA6E has genomic similarities to <jats:italic>FHIT<\/jats:italic>\/FRA3B and <jats:italic>WWOX<\/jats:italic>\/FRA16D, two other large tumor\u2010suppressor genes that are within CFS regions, we were interested in characterizing <jats:italic>Parkin<\/jats:italic> gene alterations and their possible association with cancer. After analyzing 50 cancer\u2010derived cell lines including 11 hepatocellular carcinoma (HCC) cell lines, we found that one HCC cell line, PLC\/PRF\/5, had a detectable homozygous deletion encompassing exon 3. Using quantitative duplex PCR and fluorescence in situ hybridization analysis to characterize the copy number changes of <jats:italic>Parkin<\/jats:italic> exons in HCC cell lines, we found that 4 of 11 HCC cell lines had heterozygous deletions of <jats:italic>Parkin<\/jats:italic> exons and one, Hep3B, had an exon duplication. Parkin protein expression was significantly decreased or absent in all 11 HCC cell lines. Furthermore, more than 50% of HCC primary tumors had decreased Parkin expression compared to that in normal liver tissue. <jats:italic>Parkin<\/jats:italic> gene\u2013transfected PLC5 and Hep3B cells grew more slowly than vector\u2010only transfectants and also showed increased sensitivity to apoptosis induced by cell\u2010cycle inhibitors. Therefore, we suggest that <jats:italic>Parkin<\/jats:italic> may be involved in tumor suppression and that the loss of <jats:italic>Parkin<\/jats:italic> contributes to the development of hepatocarcinoma. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20020","type":"journal-article","created":{"date-parts":[[2004,3,26]],"date-time":"2004-03-26T21:02:24Z","timestamp":1080334944000},"page":"85-96","source":"Crossref","is-referenced-by-count":107,"title":["<i>Parkin<\/i> gene alterations in hepatocellular carcinoma"],"prefix":"10.1002","volume":"40","author":[{"given":"Fang","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy","family":"Denison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Ping","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie 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