Mouse genetic background influences whether Hras G12V expression plus Cdkn2a knockdown causes angiosarcoma or undifferentiated pleomorphic sarcoma
Soft tissue sarcomas are rare mesenchymal tumours accounting for 1% of adult malignancies and are fatal in approximately one third of patients. Two of the most aggressive and lethal forms of soft tissue sarcomas are angiosarcomas and undifferentiated pleomorphic sarcomas (UPS). To examine sarcoma-re...
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Veröffentlicht in: | Oncotarget 2018-04, Vol.9 (28), p.19753 |
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Hauptverfasser: | , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Soft tissue sarcomas are rare mesenchymal tumours accounting for 1% of adult malignancies and are fatal in approximately one third of patients. Two of the most aggressive and lethal forms of soft tissue sarcomas are angiosarcomas and undifferentiated pleomorphic sarcomas (UPS). To examine sarcoma-relevant molecular pathways, we employed a lentiviral gene regulatory system to attempt to generate
models that reflect common molecular alterations of human angiosarcoma and UPS. Mice were intraveneously injected with MuLE lentiviruses expressing combinations of shRNA against
,
,
and
with or without expression of
,
or
. The systemic injection of an ecotropic lentivirus expressing oncogenic
together with the knockdown of
or
was sufficient to initiate angiosarcoma and/or UPS development, providing a flexible system to generate autochthonous mouse models of these diseases. Unexpectedly, different mouse strains developed different types of sarcoma in response to identical genetic drivers, implicating genetic background as a contributor to the genesis and spectrum of sarcomas. |
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ISSN: | 1949-2553 |