title: A combination of molecular cytogenetic analyses reveals complex genetic alterations in conventional renal cell carcinoma.
abstract: Here we report the complex pattern of genomic imbalances and rearrangements in a panel of 19 renal cell carcinoma cell lines detected with molecular cytogenetic analysis. Consistent heterogeneity in chromosome number was found, and most cell lines showed a near-triploid chromosome complement. Several cell lines showed deletions of the TP53 (alias p53), CDKN2A (alias p16), and VHL genes. Multiplex fluorescence in situ hybridization (M-FISH) analysis revealed chromosome 3 translocated to several other partners chromosomes, as well as breakage events commonly affecting chromosomes 1, 5, 8, 10, and 17. The most common abnormality detected with comparative genomic hybridization (CGH) was deletions of chromosome 3p, with loss of the RASSF1, FHIT, and p44S10 loci frequently involved. CGH gain of 5q showed overrepresentation of the EGR1 and CSF1R genes. Recurrent alterations to chromosome 7 included rearrangement of 7q11 and gains of the EGFR, TIF1, and RFC2 genes. Several lines exhibited rearrangement of 12q11 approximately q14 and overrepresentation of CDK4 and SAS loci. M-FISH revealed several other recurrent translocations, and CGH findings included loss of 9p, 14q, and 18q and gain of 8q, 12, and 20. Further genomic microarray changes included loss of MTAP, IGH@, HTR1B, and SMAD4 (previously MADH4) and gains of MYC and TOP1. An excellent correlation was observed between the genomic array and FISH data, demonstrating that this technique is effective and accurate. The aberrations detected here may reflect important pathways in renal cancer pathogenesis.
authors.affiliation: Cancer Research UK Medical Oncology Unit, Queen Mary University of London, Charterhouse Square, London, UK. jcs@soton.ac.uk
authors.forename: Jon C
authors.initials: JC
authors.lastname: Strefford
authors.forename: Irina
authors.initials: I
authors.lastname: Stasevich
authors.forename: Tim M
authors.initials: TM
authors.lastname: Lane
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Lu
authors.forename: Tim
authors.initials: T
authors.lastname: Oliver
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Young
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics*; D020732:Cytogenetic Analysis / Q000379:methods; D004273:DNA, Neoplasm; D016147:Genes, Tumor Suppressor; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008677:Metaphase; D046228:Microarray Analysis; D008967:Molecular Biology; D009693:Nucleic Acid Hybridization; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm