Array-CGH identifies cyclin D1 and UBCH10 amplicons in anaplastic thyroid carcinoma.

Abstract

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.

• Authors: Jia-Jing Lee, Amy Y M Au, Theodoros Foukakis, Michela Barbaro, Nimrod Kiss, Roderick Clifton-Bligh, Johan Staaf, Ake Borg, Leigh Delbridge, Bruce G Robinson, Göran Wallin, Anders Höög, Catharina Larsson
• Journal: Endocrine-related cancer (Endocr Relat Cancer) Vol. 15 Issue 3 Pg. 801-15 (Sep 2008) ISSN: 1351-0088 [Print] England
• PMID: 18753363 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• UBE2C protein, human
• Ubiquitin-Conjugating Enzymes
• BRAF protein, human
• Proto-Oncogene Proteins B-raf

Topics

• Aged
• Aged, 80 and over
• Carcinoma (genetics)
• Chromosomes, Human, Pair 20
• Comparative Genomic Hybridization (methods)
• Female
• Gene Amplification (physiology)
• Gene Dosage
• Gene Expression Profiling
• Genes, bcl-1
• Humans
• Male
• Middle Aged
• Mutation (physiology)
• Oligonucleotide Array Sequence Analysis (methods)
• Proto-Oncogene Proteins B-raf (genetics)
• Thyroid Neoplasms (genetics)
• Ubiquitin-Conjugating Enzymes (genetics)