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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-8-28
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1351-0088
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
801-15
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18753363-Aged, pubmed-meshheading:18753363-Aged, 80 and over, pubmed-meshheading:18753363-Carcinoma, pubmed-meshheading:18753363-Chromosomes, Human, Pair 20, pubmed-meshheading:18753363-Comparative Genomic Hybridization, pubmed-meshheading:18753363-Female, pubmed-meshheading:18753363-Gene Amplification, pubmed-meshheading:18753363-Gene Dosage, pubmed-meshheading:18753363-Gene Expression Profiling, pubmed-meshheading:18753363-Genes, bcl-1, pubmed-meshheading:18753363-Humans, pubmed-meshheading:18753363-Male, pubmed-meshheading:18753363-Middle Aged, pubmed-meshheading:18753363-Mutation, pubmed-meshheading:18753363-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:18753363-Proto-Oncogene Proteins B-raf, pubmed-meshheading:18753363-Thyroid Neoplasms, pubmed-meshheading:18753363-Ubiquitin-Conjugating Enzymes
pubmed:year
2008
pubmed:articleTitle
Array-CGH identifies cyclin D1 and UBCH10 amplicons in anaplastic thyroid carcinoma.
pubmed:affiliation
Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm, Sweden. jia.jing.lee@ki.se
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't