title: Novel candidate genes of thyroid tumourigenesis identified in Trk-T1 transgenic mice.
abstract: For an identification of novel candidate genes in thyroid tumourigenesis, we have investigated gene copy number changes in a Trk-T1 transgenic mouse model of thyroid neoplasia. For this aim, 30 thyroid tumours from Trk-T1 transgenics were investigated by comparative genomic hybridisation. Recurrent gene copy number alterations were identified and genes located in the altered chromosomal regions were analysed by Gene Ontology term enrichment analysis in order to reveal gene functions potentially associated with thyroid tumourigenesis. In thyroid neoplasms from Trk-T1 mice, a recurrent gain on chromosomal bands 1C4-E2.3 (10.0% of cases), and losses on 3H1-H3 (13.3%), 4D2.3-E2 (43.3%) and 14E4-E5 (6.7%) were identified. The genes Twist2, Ptma, Pde6d, Bmpr1b, Pdlim5, Unc5c, Srm, Trp73, Ythdf2, Taf12 and Slitrk5 are located in these chromosomal bands. Copy number changes of these genes were studied by fluorescence in situ hybridisation on 30 human papillary thyroid carcinoma (PTC) samples and altered gene expression was studied by qRT-PCR analyses in 67 human PTC. Copy number gains were detected in 83% of cases for TWIST2 and in 100% of cases for PTMA and PDE6D. DNA losses of SLITRK1 and SLITRK5 were observed in 21% of cases and of SLITRK6 in 16% of cases. Gene expression was significantly up-regulated for UNC5C and TP73 and significantly down-regulated for SLITRK5 in tumours compared with normal tissue. In conclusion, a global genomic copy number analysis of thyroid tumours from Trk-T1 transgenic mice revealed a number of novel gene alterations in thyroid tumourigenesis that are also prevalent in human PTCs.
authors.affiliation: Research Unit of Radiation Cytogenetics, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany.
authors.forename: Katrin-Janine
authors.initials: KJ
authors.lastname: Heiliger
authors.forename: Julia
authors.initials: J
authors.lastname: Hess
authors.forename: Donata
authors.initials: D
authors.lastname: Vitagliano
authors.forename: Paolo
authors.initials: P
authors.lastname: Salerno
authors.forename: Herbert
authors.initials: H
authors.lastname: Braselmann
authors.forename: Giuliana
authors.initials: G
authors.lastname: Salvatore
authors.forename: Clara
authors.initials: C
authors.lastname: Ugolini
authors.forename: Isolde
authors.initials: I
authors.lastname: Summerer
authors.forename: Tatjana
authors.initials: T
authors.lastname: Bogdanova
authors.forename: Kristian
authors.initials: K
authors.lastname: Unger
authors.forename: Gerry
authors.initials: G
authors.lastname: Thomas
authors.forename: Massimo
authors.initials: M
authors.lastname: Santoro
authors.forename: Horst
authors.initials: H
authors.lastname: Zitzelsberger
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D020917:Receptor, trkA / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics*; D055815:Young Adult
chemical_list: D020917:Receptor, trkA