Key Roles for MYC, KIT and RET signaling in secondary angiosarcomas.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4583760
- author
- 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
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- British Journal of Cancer
- volume
- 111
- issue
- 2
- pages
- 6 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:24983371
- wos:000339176300022
- scopus:84904566344
- pmid:24983371
- ISSN
- 1532-1827
- DOI
- 10.1038/bjc.2014.359
- project
- Precision Medicine in Hereditary Cancer and Sarcoma; targeted surveillance, immunotherapy and individualized follow-up
- Precision Medicine in Hereditary Cancer and Sarcoma; targeted surveillance, immunotherapy and individualized follow-up
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Department of Orthopaedics (Lund) (013028000), Pathology, (Lund) (013030000), Oncology, MV (013035000)
- id
- 5a3a2873-3aa5-41b8-92bd-0eb9731c5f1f (old id 4583760)
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- http://www.ncbi.nlm.nih.gov/pubmed/24983371?dopt=Abstract
- date added to LUP
- 2016-04-01 10:25:52
- date last changed
- 2022-03-27 08:11:26
@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 = {{https://lup.lub.lu.se/search/files/1840167/5156025}},
doi = {{10.1038/bjc.2014.359}},
volume = {{111}},
year = {{2014}},
}