Advanced

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

Lee, Jia-Jing; Au, Amy Y M; Foukakis, Theodoros; Barbaro, Michela; Kiss, Nimrod; Clifton-Bligh, Roderick; Staaf, Johan LU ; Borg, Åke LU ; Delbridge, Leigh and Robinson, Bruce G, et al. (2008) In Endocrine-Related Cancer 15(3). p.801-815
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Endocrine-Related Cancer
volume
15
issue
3
pages
801 - 815
publisher
Society for Endocrinology
external identifiers
  • wos:000259965200012
  • pmid:18753363
  • scopus:53849147531
ISSN
1479-6821
DOI
10.1677/ERC-08-0018
language
English
LU publication?
yes
id
ac3bb345-d637-4521-834d-20da3e07c0e6 (old id 1222833)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18753363?dopt=Abstract
date added to LUP
2008-09-03 11:59:25
date last changed
2017-05-28 04:32:53
@article{ac3bb345-d637-4521-834d-20da3e07c0e6,
  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.},
  author       = {Lee, Jia-Jing and Au, Amy Y M and Foukakis, Theodoros and Barbaro, Michela and Kiss, Nimrod and Clifton-Bligh, Roderick and Staaf, Johan and Borg, Åke and Delbridge, Leigh and Robinson, Bruce G and Wallin, Göran and Höög, Anders and Larsson, Catharina},
  issn         = {1479-6821},
  language     = {eng},
  number       = {3},
  pages        = {801--815},
  publisher    = {Society for Endocrinology},
  series       = {Endocrine-Related Cancer},
  title        = {Array-CGH identifies cyclin D1 and UBCH10 amplicons in anaplastic thyroid carcinoma.},
  url          = {http://dx.doi.org/10.1677/ERC-08-0018},
  volume       = {15},
  year         = {2008},
}