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A MYC and RAS co-activation signature in localized prostate cancer drives bone metastasis and castration resistance

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dc.creator Zou, Min
dc.creator Rubin, Mark A.
dc.creator Zhao, Junfei
dc.creator Kim, Jaime Yeji
dc.creator Rodriguez, Antonio
dc.creator Feng, Felix Y.
dc.creator Panja, Sukanya
dc.creator Arriaga, Juan M.
dc.creator Sims, Peter A.
dc.creator Giacobbe, Arianna
dc.creator Madubata, Chioma J.
dc.creator Mitrofanova, Antonina
dc.creator Antonarakis, Emmanuel S.
dc.creator Abate-Shen, Cory
dc.creator Alshalalfa, Mohammed
dc.creator Coleman, Ilsa
dc.creator Hibshoosh, Hanina
dc.creator Virk, Renu K.
dc.creator Rabadan, Raul
dc.creator Luo, Jun
dc.creator Ozbek, Büşra
dc.creator Ertunc, Onur
dc.creator Nelson, Peter S.
dc.creator De Marzo, Angelo M.
dc.creator Fountain, Julia
dc.creator Jeffrey Karnes, R.
dc.date 2019-12-31T21:00:00Z
dc.date.accessioned 2021-01-21T08:18:21Z
dc.date.available 2021-01-21T08:18:21Z
dc.identifier 7707a888-797c-44d9-a586-7673a421d174
dc.identifier 10.1038/s43018-020-00125-0
dc.identifier https://avesis.sdu.edu.tr/publication/details/7707a888-797c-44d9-a586-7673a421d174/oai
dc.identifier.uri http://acikerisim.sdu.edu.tr/xmlui/handle/123456789/83395
dc.description © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.Understanding the intricacies of lethal prostate cancer poses specific challenges due to difficulties in accurate modeling of metastasis in vivo. Here we show that NPKEYFP mice (for Nkx3.1CreERT2/+; Ptenflox/flox; KrasLSL-G12D/+; R26R-CAG-LSL-EYFP/+) develop prostate cancer with a high penetrance of metastasis to bone, thereby enabling detection and tracking of bone metastasis in vivo and ex vivo. Transcriptomic and whole-exome analyses of bone metastasis from these mice revealed distinct molecular profiles conserved between human and mouse and specific patterns of subclonal branching from the primary tumor. Integrating bulk and single-cell transcriptomic data from mouse and human datasets with functional studies in vivo unravels a unique MYC/RAS co-activation signature associated with prostate cancer metastasis. Finally, we identify a gene signature with prognostic value for time to metastasis and predictive of treatment response in human patients undergoing androgen receptor therapy across clinical cohorts, thus uncovering conserved mechanisms of metastasis with potential translational significance.
dc.language eng
dc.rights info:eu-repo/semantics/closedAccess
dc.title A MYC and RAS co-activation signature in localized prostate cancer drives bone metastasis and castration resistance
dc.type info:eu-repo/semantics/article


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