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Anaplastic thyroid cancer (ATC) is a rare but highly aggressive disease with largely unexplained etiology and molecular pathogenesis. In this study, we analyzed genome-wide copy number changes, BRAF (V-raf sarcoma viral oncogene homolog B1) mutations, and p16 and cyclin D1 expressions in a panel of ATC primary tumors. Three ATCs harbored the common BRAF mutation V600E. Using array-comparative genomic hybridisation (array-CGH), several distinct recurrent copy number alterations were revealed including gains in 16p11.2, 20q11.2, and 20q13.12. Subsequent fluorescence in situ hybridization revealed recurrent locus gain of UBCH10 in 20q13.12 and Cyclin D1 (CCND1) in 11q13. The detection of a homozygous loss encompassing the CDKN2A locus in 9p21.3 motivated the examination of p16 protein expression, which was undetectable in 24/27 ATCs (89%). Based on the frequent gain in 11q13 (41%; n=11), the role of CCND1 was further investigated. Expression of cyclin D1 protein was observed at varying levels in 18/27 ATCs (67%). The effect of CCND1 on thyroid cell proliferation was assessed in vitro in ATC cells by means of siRNA and in thyroid cells after CCND1 transfection. In summary, the recurrent chromosomal copy number changes and molecular alterations identified in this study may provide an insight into the pathogenesis and development of ATC. [ABSTRACT FROM AUTHOR]

Objective: To identify molecular markers useful for the diagnostic discrimination of benign and malignant follicular thyroid tumors. Methods: A panel of thyroid tumors was characterized with expression profiling using cDNA microarrays. A robust algorithm for gene selection was developed to identify molecular markers useful for the classification of heterogeneous tumor classes. The study included tumor tissue specimens from 10 patients with benign follicular adenomas and from 10 with malignant tumors. The malignant tumors mainly consisted of clinically relevant minimally invasive follicular carcinomas. The mRNA expression level of a candidate gene, FHL1, was evaluated in an independent series of 61 tumors. Results: 22 gene expression markers were identified as differentially expressed. Several of the identified genes, for example DIO1, CITED1, CA12 and FN1, have previously been observed as differentially expressed in various thyroid tumors. FHL1 was significantly underexpressed in carcinomas compared to adenomas in the independent panel of tumors. The results indicate that a small number of genes can be useful to distinguish follicular adenomas from follicular carcinomas. Conclusions: Our findings clearly corroborate previous studies and identify novel candidate molecular markers. These genes have the potential for molecular classification of follicular thyroid tumors and for providing improved understanding of the molecular mechanisms involved in thyroid malignancies. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In this study we present two novel anaplastic thyroid carcinoma (ATC) lines (HTh 104 and HTh 112) and further characterize six frequently used ATC lines (HTh 7, HTh 74, HTh 83, C 643, KAT-4, and SW 1736). Three of the lines carried a heterozygous BRAFmutation V600E, which is in line with reports of BRAFmutations in primary ATC and papillary thyroid cancer. Several nonrandom breakpoints were identified by spectral karyotyping (SKY) and G-banding in these lines including the novel 1p36 and 17q24-25 as well as 3p21-22 and 15q26 that are also implicated in well-differentiated thyroid cancers. Comparative genomic hybridization showed frequent gain of 20q, including the UBCH10gene in 20q13.12, which was further confirmed by array-comparative genomic hybridization and fluorescence in situhybridization analyses. Our results concur with previous studies in both primary tumors and cell lines, indicating that gain of chromosome 20 is important in the pathogenesis of ATC and/or progression of differentiated thyroid cancers to ATC. [ABSTRACT FROM AUTHOR]