{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:06:05Z","timestamp":1791216365409,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,6,16]],"date-time":"2003-06-16T00:00:00Z","timestamp":1055721600000},"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;amp; Cancer"],"published-print":{"date-parts":[[2003,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Characterization of FRA6E (6q26), the third most frequently observed common fragile site (CFS) in the human population, determined that aphidicolin\u2010induced instability at FRA6E extends over a very large region (3.6 Mb). Sequence analysis identified eight genes (<jats:italic>IGF2R<\/jats:italic>, <jats:italic>SLC22A1<\/jats:italic>, <jats:italic>SLC22A2<\/jats:italic>, <jats:italic>SLC22A3<\/jats:italic>, <jats:italic>PLG<\/jats:italic>, <jats:italic>LPA<\/jats:italic>, <jats:italic>MAP3K4<\/jats:italic>, and <jats:italic>PARK2<\/jats:italic>) as mapping within the large FRA6E region. <jats:italic>PARK2<\/jats:italic>, the gene associated with autosomal recessive juvenile parkinsonism (ARJP), accounts for more than half of the CFS. Homozygous deletions and large heterozygous deletions have been observed in <jats:italic>PARK2<\/jats:italic> in ARJP patients. RT\u2010PCR analysis of the eight genes localizing to FRA6E indicated that 50% of the genes, including <jats:italic>PARK2<\/jats:italic>, were down\u2010regulated in one or more of the primary ovarian tumors analyzed. <jats:italic>PARK2<\/jats:italic> expression was down\u2010regulated in 60.0% of the primary ovarian tumors analyzed. Additionally, we found tumor\u2010specific alternative transcripts of <jats:italic>PARK2<\/jats:italic>. Loss of heterozygosity analysis of primary ovarian tumors by use of polymorphic markers in the 6q26 region demonstrated 72% LOH in the center of the <jats:italic>PARK2<\/jats:italic> gene, the highest of any of the markers tested. FRA6E shares many similarities with FRA3B (3p14.2) and FRA16D (16q23.2) in representing a large region of genomic instability and containing an extremely large gene that may play a role in the development of ovarian and many other cancers. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.10236","type":"journal-article","created":{"date-parts":[[2003,7,17]],"date-time":"2003-07-17T10:09:30Z","timestamp":1058436570000},"page":"40-52","source":"Crossref","is-referenced-by-count":130,"title":["Characterization of FRA6E and its potential role in autosomal recessive juvenile parkinsonism and ovarian cancer"],"prefix":"10.1002","volume":"38","author":[{"given":"Stacy R.","family":"Denison","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwen","family":"Callahan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole 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