title: Array CGH demonstrates characteristic aberration signatures in human papillary thyroid carcinomas governed by RET/PTC.
abstract: The aim of this study is to investigate additional genetic alterations in papillary thyroid carcinomas (PTCs) with known RET/PTC rearrangements. We applied array-based comparative genomic hybridization (array CGH) to 33 PTC (20 PTC from adults, 13 post-Chernobyl PTC from children) with known RET/PTC status. Principal component analysis and hierarchical cluster analysis identified cases with similar aberration patterns. Significant deviations between tumour-groups were obtained by statistical testing (Fisher's exact test in combination with Benjamini-Hochberg FDR-controlling procedure). FISH analysis on FFPE sections was applied to validate the array CGH data. Deletions were found more frequently in RET/PTC-positive and RET/PTC-negative tumours than amplifications. Specific aberration signatures were identified that discriminated between RET/PTC-positive and RET/PTC-negative cases (aberrations on chromosomes 1p, 3q, 4p, 7p, 9p/q, 10q, 12q, 13q and 21q). In addition, childhood and adult RET/PTC-positive cases differ significantly for a deletion on the distal part of chromosome 1p. There are additional alterations in RET/PTC-positive tumours, which may act as modifiers of RET activation. In contrast, alterations in RET/PTC-negative tumours indicate alternative routes of tumour development. The data presented serve as a starting point for further studies on gene expression and function of genes identified in this study.
authors.affiliation: Institut für Molekulare Strahlenbiologie, Helmholtz Zentrum München-Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Unger
authors.forename: E
authors.initials: E
authors.lastname: Malisch
authors.forename: G
authors.initials: G
authors.lastname: Thomas
authors.forename: H
authors.initials: H
authors.lastname: Braselmann
authors.forename: A
authors.initials: A
authors.lastname: Walch
authors.forename: G
authors.initials: G
authors.lastname: Jackl
authors.forename: P
authors.initials: P
authors.lastname: Lewis
authors.forename: E
authors.initials: E
authors.lastname: Lengfelder
authors.forename: T
authors.initials: T
authors.lastname: Bogdanova
authors.forename: J
authors.initials: J
authors.lastname: Wienberg
authors.forename: H
authors.initials: H
authors.lastname: Zitzelsberger
mesh_terms: D000293:Adolescent; D000328:Adult; D002291:Carcinoma, Papillary / Q000235:genetics*; D047852:Chernobyl Nuclear Accident; D002648:Child; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*; D000070584:Tripartite Motif Proteins
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C064419:TRIM27 protein, human; D000070584:Tripartite Motif Proteins