title: 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.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm, Sweden. jia.jing.lee@ki.se
authors.forename: Jia-Jing
authors.initials: JJ
authors.lastname: Lee
authors.forename: Amy Y M
authors.initials: AY
authors.lastname: Au
authors.forename: Theodoros
authors.initials: T
authors.lastname: Foukakis
authors.forename: Michela
authors.initials: M
authors.lastname: Barbaro
authors.forename: Nimrod
authors.initials: N
authors.lastname: Kiss
authors.forename: Roderick
authors.initials: R
authors.lastname: Clifton-Bligh
authors.forename: Johan
authors.initials: J
authors.lastname: Staaf
authors.forename: Ake
authors.initials: A
authors.lastname: Borg
authors.forename: Leigh
authors.initials: L
authors.lastname: Delbridge
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Robinson
authors.forename: Göran
authors.initials: G
authors.lastname: Wallin
authors.forename: Anders
authors.initials: A
authors.lastname: Höög
authors.forename: Catharina
authors.initials: C
authors.lastname: Larsson