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

Emelie Styring, J Seinen, Mev Dominguez, Henryk Domanski, Mats Jönsson, Fredrik Vult von Steyern, H J Hoekstra, A J H Suurmeijer, Mef Nilbert

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

19 Citeringar (SciVal)
153 Nedladdningar (Pure)

Sammanfattning

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.
Originalspråkengelska
Sidor (från-till)407-412
Antal sidor6
TidskriftBritish Journal of Cancer
Volym111
Nummer2
DOI
StatusPublished - 2014

Bibliografisk information

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)

Ämnesklassifikation (UKÄ)

  • Cancer och onkologi

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