title: Genome-wide copy number profiling using a 100K SNP array reveals novel disease-related genes BORIS and TSHZ1 in juvenile angiofibroma.
abstract: Juvenile angiofibroma (JA) is a unique fibrovascular tumor, which is almost exclusively found in the posterior nasal cavity of adolescent males. Although histologically classified as benign, the tumor often shows an aggressive growth pattern and has been associated with chromosomal imbalances, amplification of oncogenes and epigenetic dysregulation. We present the first genome-wide profiling of JAs (n=14) with a 100K single nucleotide polymorphism (SNP) microarray. Among the 30 novel JA-specific amplifications detected on autosomal chromosomes with this technique, the genes encoding the cancer-testis antigen BORIS (brother of the regulator of imprinted sites) and the developmental regulator protein TSHZ1 (teashirt zinc finger homeobox 1) were selected for further analysis. Gains for both BORIS (20q13.3) and TSHZ1 (18q22.3) were confirmed by quantitative genomic PCR. Furthermore, quantitative RT-PCR revealed a significant up-regulation of BORIS (p<0.001) and TSHZ1 transcripts (p<0.05) for JAs compared to nasal mucosa. Following detection of BORIS and TSHZ1 proteins in western blots of JAs, subcellular localization was determined for both proteins in immunostaining of JA cryosections. In conclusion, genomic copy number profiling using an SNP microarray has been proven to be a suitable and reliable tool for identifying novel disease-related genes in JAs and newly implicates BORIS and TSHZ1 overexpression in the pathogenesis of JAs. Detection of BORIS in JAs is described with special regard to tumor proliferation and epigenetic dysregulation, and the finding of TSHZ1 amplifications is discussed with special respect to the hypothesis of JAs as malformations of the first branchial arch artery.
authors.affiliation: Department of Otorhino-laryngology, Saarland University Medical Center, D-66421 Homburg, Germany. bernhard.schick@uks.eu
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schick
authors.forename: Silke
authors.initials: S
authors.lastname: Wemmert
authors.forename: Vivienne
authors.initials: V
authors.lastname: Willnecker
authors.forename: Julia
authors.initials: J
authors.lastname: Dlugaiczyk
authors.forename: Piero
authors.initials: P
authors.lastname: Nicolai
authors.forename: Henryk
authors.initials: H
authors.lastname: Siwiec
authors.forename: Christian T
authors.initials: CT
authors.lastname: Thiel
authors.forename: Anita
authors.initials: A
authors.lastname: Rauch
authors.forename: Olaf
authors.initials: O
authors.lastname: Wendler
mesh_terms: D018322:Angiofibroma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D009669:Nose Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C456540:CTCFL protein, human; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C569098:TSHZ1 protein, human