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Key Roles for MYC, KIT and RET signaling in secondary angiosarcomas.

Styring, Emelie LU ; Seinen, J; Dominguez, Mev LU ; Domanski, Henryk LU ; Jönsson, Mats LU ; Vult von Steyern, Fredrik LU ; Hoekstra, H J; Suurmeijer, A J H and Nilbert, Mef LU (2014) In British Journal of Cancer 111(2). p.407-412
Abstract
Background:Angiosarcomas may develop as primary tumours of unknown cause or as secondary tumours, most commonly following radiotherapy to the involved field. The different causative agents may be linked to alternate tumorigenesis, which led us to investigate the genetic profiles of morphologically indistinguishable primary and secondary angiosarcomas.Methods:Whole-genome (18k) c-DNA-mediated annealing, selection, extension and ligation analysis was used to genetically profile 26 primary and 29 secondary angiosarcomas. Key findings were thereafter validated using RT-qPCR, immunohistochemistry and validation of the gene signature to an external data set.Results:In total, 103 genes were significantly deregulated between primary and secondary... (More)
Background:Angiosarcomas may develop as primary tumours of unknown cause or as secondary tumours, most commonly following radiotherapy to the involved field. The different causative agents may be linked to alternate tumorigenesis, which led us to investigate the genetic profiles of morphologically indistinguishable primary and secondary angiosarcomas.Methods:Whole-genome (18k) c-DNA-mediated annealing, selection, extension and ligation analysis was used to genetically profile 26 primary and 29 secondary angiosarcomas. Key findings were thereafter validated using RT-qPCR, immunohistochemistry and validation of the gene signature to an external data set.Results:In total, 103 genes were significantly deregulated between primary and secondary angiosarcomas. Secondary angiosarcomas showed upregulation of MYC, KIT and RET and downregulation of CDKN2C. Functional annotation analysis identified multiple target genes in the receptor protein tyrosine kinase pathway. The results were validated using RT-qPCR and immunohistochemistry. Further, the gene signature was applied to an external data set and, herein, distinguished primary from secondary angiosarcomas.Conclusions:Upregulation of MYC, KIT and RET and downregulation of CDKN2C characterise secondary angiosarcoma, which implies possibilities for diagnostic application and a mechanistic basis for therapeutic evaluation of RET-kinase-inhibitors in these highly aggressive tumours. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Cancer
volume
111
issue
2
pages
407 - 412
publisher
Nature Publishing Group
external identifiers
  • pmid:24983371
  • wos:000339176300022
  • scopus:84904566344
ISSN
1532-1827
DOI
10.1038/bjc.2014.359
language
English
LU publication?
yes
id
5a3a2873-3aa5-41b8-92bd-0eb9731c5f1f (old id 4583760)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24983371?dopt=Abstract
date added to LUP
2014-08-06 21:33:59
date last changed
2017-11-12 03:07:47
@article{5a3a2873-3aa5-41b8-92bd-0eb9731c5f1f,
  abstract     = {Background:Angiosarcomas may develop as primary tumours of unknown cause or as secondary tumours, most commonly following radiotherapy to the involved field. The different causative agents may be linked to alternate tumorigenesis, which led us to investigate the genetic profiles of morphologically indistinguishable primary and secondary angiosarcomas.Methods:Whole-genome (18k) c-DNA-mediated annealing, selection, extension and ligation analysis was used to genetically profile 26 primary and 29 secondary angiosarcomas. Key findings were thereafter validated using RT-qPCR, immunohistochemistry and validation of the gene signature to an external data set.Results:In total, 103 genes were significantly deregulated between primary and secondary angiosarcomas. Secondary angiosarcomas showed upregulation of MYC, KIT and RET and downregulation of CDKN2C. Functional annotation analysis identified multiple target genes in the receptor protein tyrosine kinase pathway. The results were validated using RT-qPCR and immunohistochemistry. Further, the gene signature was applied to an external data set and, herein, distinguished primary from secondary angiosarcomas.Conclusions:Upregulation of MYC, KIT and RET and downregulation of CDKN2C characterise secondary angiosarcoma, which implies possibilities for diagnostic application and a mechanistic basis for therapeutic evaluation of RET-kinase-inhibitors in these highly aggressive tumours.},
  author       = {Styring, Emelie and Seinen, J and Dominguez, Mev and Domanski, Henryk and Jönsson, Mats and Vult von Steyern, Fredrik and Hoekstra, H J and Suurmeijer, A J H and Nilbert, Mef},
  issn         = {1532-1827},
  language     = {eng},
  number       = {2},
  pages        = {407--412},
  publisher    = {Nature Publishing Group},
  series       = {British Journal of Cancer},
  title        = {Key Roles for MYC, KIT and RET signaling in secondary angiosarcomas.},
  url          = {http://dx.doi.org/10.1038/bjc.2014.359},
  volume       = {111},
  year         = {2014},
}