University Of Tasmania

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Spontaneous tumor regression in Tasmanian devils associated with RASL11A activation

journal contribution
posted on 2023-05-20, 20:08 authored by Margres, MJ, Ruiz Aravena, M, Rodrigo Hamede RossRodrigo Hamede Ross, Chawla, K, Patton, AH, Lawrance, MF, Fraik, AK, Stahlke, AR, Davis, BW, Ostrander, EA, Menna JonesMenna Jones, McCallum, H, Paddison, PJ, Hohenlohe, PA, Hockenbery, D, Storfer, A
Spontaneous tumor regression has been documented in a small proportion of human cancer patients, but the specificmechanisms underlying tumor regression without treatment are not well understood. Tasmanian devils are threatened with extinctionfrom a transmissible cancer due to universal susceptibility and a near 100% case fatality rate. In over 10,000 cases, <20 instances ofnatural tumor regression have been detected. Previous work in this system has focused on Tasmanian devil genetic variation associatedwith the regression phenotype. Here, we used comparative and functional genomics to identify tumor genetic variation associated withtumor regression. We show that a single point mutation in the 5' untranslated region of the putative tumor suppressor RASL11Asignificantly contributes to tumor regression. RASL11A was expressed in regressed tumors but silenced in wild-type, nonregressedtumors, consistent with RASL11A downregulation in human cancers. Induced RASL11A expression significantly reduced tumor cellproliferation in vitro. The RAS pathway is frequently altered in human cancers, and RASL11A activation may provide a therapeutictreatment option for Tasmanian devils as well as a general mechanism for tumor inhibition.


National Institutes of Health


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School of Natural Sciences


Oxford University Press

Place of publication

United States

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Copyright © 2020 by the Genetics Society of America

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Socio-economic Objectives

Control of pests, diseases and exotic species in terrestrial environments