Key Roles for MYC, KIT and RET signaling in secondary angiosarcomas
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Key Roles for MYC, KIT and RET signaling in secondary angiosarcomas. / Styring, E; Seinen, J; Dominguez-Valentin, M; Domanski, H A; Jönsson, M; von Steyern, F V; Hoekstra, H J; Suurmeijer, A J H; Nilbert, M.
I: B J C, Bind 111, Nr. 2, 15.07.2014, s. 407-412.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Key Roles for MYC, KIT and RET signaling in secondary angiosarcomas
AU - Styring, E
AU - Seinen, J
AU - Dominguez-Valentin, M
AU - Domanski, H A
AU - Jönsson, M
AU - von Steyern, F V
AU - Hoekstra, H J
AU - Suurmeijer, A J H
AU - Nilbert, M
PY - 2014/7/15
Y1 - 2014/7/15
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Child
KW - Child, Preschool
KW - Female
KW - Gene Amplification
KW - Genes, myc
KW - Genome, Human
KW - Hemangiosarcoma
KW - Humans
KW - Immunohistochemistry
KW - Male
KW - Middle Aged
KW - Neoplasms, Second Primary
KW - Proto-Oncogene Proteins c-kit
KW - Proto-Oncogene Proteins c-ret
KW - Young Adult
U2 - 10.1038/bjc.2014.359
DO - 10.1038/bjc.2014.359
M3 - Journal article
C2 - 24983371
VL - 111
SP - 407
EP - 412
JO - The British journal of cancer. Supplement
JF - The British journal of cancer. Supplement
SN - 0007-0920
IS - 2
ER -
ID: 138142471