title: Patterns of aneuploidy in stage IV clear cell renal cell carcinoma revealed by comparative genomic hybridization and spectral karyotyping.
abstract: We report the use of spectral karyotyping (SKY) and comparative genomic hybridization (CGH) to describe the numerous genomic imbalances characteristic of stage IV clear cell renal cell carcinoma (CCRCC). SKY and CGH were performed on 10 cell lines established from nephrectomy specimens, and CGH on uncultured material from five of the primary renal tumors. The mutational status of VHL (3p25) and MET (7q31), genes implicated in renal carcinogenesis, were determined for each case. Each case showed marked aneuploidy, with an average number of copy alterations of 14.6 (+/-2.7) in the primary tumors and 19.3 (+/-4.6) in the cell lines. Both whole-chromosome and chromosome-segment imbalances were noted by CGH: consistent losses or gains included +5q23-->ter (100%), -3p14-->ter (80%), and +7 (70%). All VHL mutations and 83% of the genomic imbalances found in the primary tumors were also found in the cell lines derived from them. SKY showed many complex structural rearrangements that were undetected by conventional banding analysis in these solid tumors. All cases with VHL inactivation had 3p loss and 5q gain related primarily to unbalanced translocations between 3p and 5q. In contrast, gains of chromosome 7 resulted primarily from whole-chromosome gains and were not associated with mutations of MET. SKY and CGH demonstrated that genomic imbalances in advanced RCC were the result of either segregation errors [i.e., whole chromosomal gains and losses (7.8/case)] or chromosomal rearrangements (10.7/case), of which the majority were unbalanced translocations.
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Pavlovich
authors.forename: Hesed
authors.initials: H
authors.lastname: Padilla-Nash
authors.forename: Danny
authors.initials: D
authors.lastname: Wangsa
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nickerson
authors.forename: Vera
authors.initials: V
authors.lastname: Matrosova
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
authors.forename: Thomas
authors.initials: T
authors.lastname: Ried
authors.forename: John L
authors.initials: JL
authors.lastname: Phillips
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics*; D000782:Aneuploidy; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D002872:Chromosome Deletion; D020223:Chromosome Painting; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D007621:Karyotyping; D007680:Kidney Neoplasms / Q000235:genetics*; D008025:Ligases / Q000235:genetics; D008297:Male; D009367:Neoplasm Staging; D009693:Nucleic Acid Hybridization / Q000379:methods; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein
chemical_list: D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D019859:Proto-Oncogene Proteins c-met; D008025:Ligases; C497446:VHL protein, human