Array CGH demonstrates characteristic aberration signatures in human papillary thyroid carcinomas governed by RET/PTC.
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.
Unger
K
K
Institut für Molekulare Strahlenbiologie, Helmholtz Zentrum München-Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH, Germany.
Malisch
E
E
Thomas
G
G
Braselmann
H
H
Walch
A
A
Jackl
G
G
Lewis
P
P
Lengfelder
E
E
Bogdanova
T
T
Wienberg
J
J
Zitzelsberger
H
H
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
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C064419:TRIM27 protein, human; D000070584:Tripartite Motif Proteins