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Evidence That STK19 Is Not an NRAS-dependent Melanoma Driver

Rodríguez-Martínez, M; Boissiére, T; Gonzalez, MN; Litchfield, K; Mitter, R; Walker, J; Kjœr, S; ... Svejstrup, JQ; + view all (2020) Evidence That STK19 Is Not an NRAS-dependent Melanoma Driver. Cell , 181 (6) 1395-1405.e11. 10.1016/j.cell.2020.04.014. Green open access

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Abstract

STK19 was proposed to be a cancer driver, and recent work by Yin et al. (2019) in Cell suggested that the frequently recurring STK19 D89N substitution represents a gain-of-function change, allowing increased phosphorylation of NRAS to enhance melanocyte transformation. Here we show that the STK19 gene has been incorrectly annotated, and that the expressed protein is 110 amino acids shorter than indicated by current databases. The "cancer driving" STK19 D89N substitution is thus outside the coding region. We also fail to detect evidence of the mutation affecting STK19 expression; instead, it is a UV signature mutation, found in the promoter of other genes as well. Furthermore, STK19 is exclusively nuclear and chromatin-associated, while no evidence for it being a kinase was found. The data in this Matters Arising article raise fundamental questions about the recently proposed role for STK19 in melanoma progression via a function as an NRAS kinase, suggested by Yin et al. (2019) in Cell. See also the response by Yin et al. (2020), published in this issue.

Type: Article
Title: Evidence That STK19 Is Not an NRAS-dependent Melanoma Driver
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cell.2020.04.014
Publisher version: http://doi.org/10.1016/j.cell.2020.04.014
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10102439
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