{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T15:40:10Z","timestamp":1700408410224},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2001,3,7]],"date-time":"2001-03-07T00:00:00Z","timestamp":983923200000},"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":[[2001,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Deletions of 3p25, gains of chromosomes 7 and 10, and isochromosome 17q are known cytogenetic aberrations in sporadic renal cell carcinoma (RCC). In addition, a majority of RCCs have loss of heterozygosity (LOH) of the Von Hippel\u2010Lindau (<jats:italic>VHL<\/jats:italic>) gene located at chromosome band 3p25. Patients who inherit a germline mutation of the <jats:italic>VHL<\/jats:italic> gene can develop multifocal RCCs and other solid tumors, including malignancies of the pancreas, adrenal medulla, and brain. VHL tumors follow the two\u2010hit model of tumorigenesis, as LOH of <jats:italic>VHL<\/jats:italic>, a classic tumor suppressor gene, is the critical event in the development of the neoplastic phenotype. In an attempt to define the cytogenetic aberrations from early tumors to late RCC further, we applied spectral karyotyping (SKY) to 23 renal tumors harvested from 6 unrelated VHL patients undergoing surgery. Cysts and low\u2010grade solid lesions were near\u2010diploid and contained 1\u20132 reciprocal translocations, dicentric chromosomes, and\/or isochromosomes. A variety of sole numerical aberrations included gains of chromosomes 1, 2, 4, 7, 10, 13, 21, and the X chromosome, although no tumors had sole numerical losses. Three patients shared a breakpoint at 2p21\u201322, and three others shared a dicentric chromosome 9 or an isochromosome 9q. In contrast to the near\u2010diploidy of the low\u2010grade lesions, a high\u2010grade lesion and its nodal metastasis were markedly aneuploid, revealed loss of <jats:italic>VHL<\/jats:italic> by fluorescence in situ hybridization (FISH), and contained recurrent unbalanced translocations and losses of chromosome arms 2q, 3p, 4q, 9p, 14q, and 19p as demonstrated by comparative genomic hybridization (CGH). By combining SKY, CGH, and FISH of multiple tumors from the same VHL kidney, we have begun to identify chromosomal aberrations in the earliest stages of VHL\u2010related renal cell tumors. Our current findings illustrate the cytogenetic heterogeneity of different VHL lesions from the same kidney, which supports the multiclonal origins of hereditary RCCs. Published 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.1111","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T21:30:12Z","timestamp":1030311012000},"page":"1-9","source":"Crossref","is-referenced-by-count":21,"title":["Molecular cytogenetic characterization of early and late renal cell carcinomas in Von Hippel\u2010Lindau disease"],"prefix":"10.1002","volume":"31","author":[{"given":"John L.","family":"Phillips","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. 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