title: Comparative genomic hybridization shows complex genomic changes of plasmacytoid urothelial carcinoma.
abstract: OBJECTIVE
  To describe genomic imbalances in plasmacytoid urothelial carcinoma (PUC), which is a rare and aggressive variant of urothelial carcinoma (UC).
  
  
  METHODS
  In total, 25 formalin-fixed paraffin-embedded PUCs were analyzed by metaphase comparative genomic hybridization. Genomic imbalances were considered to be characteristic if they were detected in ≥ 20% of the cases. Chromosome regions deviating by ≥ 3 standard deviations from the average chromosome profile were scored as chromosomal gains or losses. Copy-number variations (CNVs) of CDH1 (16q 22.1), SNAI1 (20q 13.1), CCND1 (11q13.3), ERBB2 (17q12), and FOXO3 (6q21) were validated using quantitative polymerase chain reaction.
  
  
  RESULTS
  Chromosomal aberrations were detected in every PUC analyzed, and the average number of aberrations was 10.24 (ranging from 1-15). Characteristic aberrations were gains on 1q (48%), 3p (20%), 6p (32%), 11q (72%), 15q (36%), 16q (44%), 17p (76%), 17q (88%), and 20q (88%) and losses on 2q (24%) 4p (36%), 4q (84%), 5q (44%), 6q (68%), 13q (20%), and Xq (52%). polymerase chain reaction-based analysis of CNV for CCND1 (11q13) showed a deletion in 73% of the cases. CDH1 (16q22) was deleted in 72% and amplified in 5%. ERBB2 (17q12) displayed remarkably few copy-number alterations, with only 14% showing an amplification. SNAI1 (20q13) showed reduced gene copy numbers in 59.1% of the cases, whereas no copy-number gains were detected. FOXO3 (6q21) exhibited the lowest number of copy-number alterations, with 9% of all cases showing an amplification.
  
  
  CONCLUSIONS
  In PUCs, the frequency of aneuploidy and the complexity of genomic changes per tumor are greater than those described in conventional UC. The aberrations described in PUC involve the same regions that are associated with aggressive biological behavior in conventional UC. Gains on 11q, 17q, 17p, and 20q and losses on 4q and 6q affect most PUCs and seem to harbor important chromosomal regions for PUC carcinogenesis. Large-scale deletions on chromosome 9 were not detected. CNV analysis indicates heterozygous deletion of CDH1 as one underlying mechanism of loss of membranous E-cadherin in PUC. Loss of CCND1 and SNAI1 is a common molecular feature and could contribute to the aggressive biological behavior of PUC.
authors.affiliation: Department of Urology, University Hospital Erlangen, Erlangen, Germany. Electronic address: Bastian.Keck@uk-erlangen.de.
authors.forename: Bastian
authors.initials: B
authors.lastname: Keck
authors.affiliation: Department of Urology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Ellmann
authors.affiliation: Department of Pathology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Stoehr
authors.affiliation: Department of Urology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Weigelt
authors.affiliation: Department of Urology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goebell
authors.affiliation: Department of Urology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Kunath
authors.affiliation: Department of Urology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Helge
authors.initials: H
authors.lastname: Taubert
authors.affiliation: Department of Pathology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: Department of Urology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Wullich
authors.affiliation: Department of Urology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Wach
mesh_terms: D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization / Q000379:methods; D056915:DNA Copy Number Variations; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D016612:Paraffin Embedding; D014571:Urologic Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm
keywords: Comparative genomic hybridization; Copy-number variation; Plasmacytoid; Urothelial neoplasms