title: Homozygous losses detected by array comparative genomic hybridization in multiplex urothelial carcinomas of the bladder.
abstract: Urothelial carcinomas (UCs) may present at first as a solitary or multifocal neoplasm. We applied high resolution array comparative genomic hybridization to 24 solitary and 32 multiplex UCs and used the hidden Markov model algorithm to identify the copy number changes at the probe level. Copy number losses and homozygous deletions at the chromosome 9p region affecting the CDKN2A and MTAP genes were the most frequent alterations in both groups of tumors. We have delineated two new tumor suppressor gene regions at chromosome 9p that harbor the PTPRD and BNC2 genes. Copy number losses at chromosomal regions 2q, 8p, and 18p occurred preferentially in solitary UCs, whereas multiplex UCs displayed loss of large chromosomal regions at 9q, 10q, 11q, 18q, and 21q. Homozygous deletions harboring loci of cell adhesion genes such as claudins, desmocollins, and desmogleins were seen exclusively in multiplex UCs. Amplifications occurred only in invasive G3 UCs irrespective of staging. Our study suggests that solitary and multiplex UCs may have divergent genetic pathways. The biallelic inactivation of cellular adhesion genes by homozygous deletions in multiplex UCs may explain the frequent intravesical spreading of tumor cells. .
authors.affiliation: Department of Urology, Medical School, University of Pécs, Pécs, Hungary.
authors.forename: Tamas
authors.initials: T
authors.lastname: Beothe
authors.affiliation: Department of Forensic Molecular Biology, Erasmus University Medical Centre, Rotterdam, Netherlands.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Zubakov
authors.affiliation: Department of Urology, Medical School, University of Pécs, Pécs, Hungary; Medical Faculty, Ruprecht-Karls University, Heidelberg, Germany. Electronic address: G.Kovacs@gmx.de.
authors.forename: Gyula
authors.initials: G
authors.lastname: Kovacs
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D002448:Cell Adhesion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D055028:Comparative Genomic Hybridization / Q000379:methods*; D056915:DNA Copy Number Variations; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics; D017384:Sequence Deletion; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: C484527:BNC2 protein, human; D004268:DNA-Binding Proteins; C090899:PTPRD protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2
keywords: array comparative genomic hybridization; cell adhesion; homozygous loss; multiplex tumors; urothelial carcinoma