title: c-myc copy number gains in bladder cancer detected by fluorescence in situ hybridization.
abstract: Amplification and overexpression of c-myc have been suggested as prognostic markers in human cancer. To assess the role of c-myc gene copy number alterations in bladder cancer, 87 bladder tumors were examined for c-myc aberrations by fluorescence in situ hybridization. Dual labeling hybridization with a repetitive pericentromeric probe specific for chromosome 8 and a probe for the c-myc locus (at 8q24) was performed to analyze c-myc copy number in relation to chromosome 8 copy number on a cell by cell basis. A clear-cut c-myc amplification (up to 40 to 150 copies per cell) was found in 3 tumors. There was a low level c-myc copy number increase in 32 of the remaining 84 tumors. There was no association of low level c-myc copy number increase with c-myc protein overexpression. This suggests that a c-myc gene copy number gain as detected by fluorescence in situ hybridization does not necessarily reflect a disturbed c-myc gene function but may indicate a structural chromosome 8 abnormality including gain of distal 8q. The strong association of low level c-myc (8q) gains with tumor grade (P < 0.0001), stage (P < 0.0001), chromosome polysomy (P < 0.0001), p53 protein expression (P = 0.0019), p53 deletion (P = 0.0403), and tumor cell proliferation (Ki67 labeling index; P = 0.0021) is consistent with a role of chromosome 8 alterations in bladder cancer progression.
authors.affiliation: Department of Laboratory Medicine, University of California, San Francisco, USA.
authors.forename: G
authors.initials: G
authors.lastname: Sauter
authors.forename: P
authors.initials: P
authors.lastname: Carroll
authors.forename: H
authors.initials: H
authors.lastname: Moch
authors.forename: A
authors.initials: A
authors.lastname: Kallioniemi
authors.forename: R
authors.initials: R
authors.lastname: Kerschmann
authors.forename: P
authors.initials: P
authors.lastname: Narayan
authors.forename: M J
authors.initials: MJ
authors.lastname: Mihatsch
authors.forename: F M
authors.initials: FM
authors.lastname: Waldman
mesh_terms: D002898:Chromosomes, Human, Pair 8; D005784:Gene Amplification / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins / Q000032:analysis; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
chemical_list: D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53