eCite Digital Repository

Spontaneous tumor regression in Tasmanian devils associated with RASL11A activation

Citation

Margres, MJ and Ruiz Aravena, M and Hamede, R and Chawla, K and Patton, AH and Lawrance, MF and Fraik, AK and Stahlke, AR and Davis, BW and Ostrander, EA and Jones, ME and McCallum, H and Paddison, PJ and Hohenlohe, PA and Hockenbery, D and Storfer, A, Spontaneous tumor regression in Tasmanian devils associated with RASL11A activation, Genetics, 215, (4) pp. 1143-1152. ISSN 1943-2631 (2020) [Refereed Article]


Preview
PDF
Pending copyright assessment - Request a copy
1Mb
  

DOI: doi:10.1534/genetics.120.303428

Abstract

Spontaneous tumor regression has been documented in a small proportion of human cancer patients, but the specific mechanisms underlying tumor regression without treatment are not well understood. Tasmanian devils are threatened with extinction from a transmissible cancer due to universal susceptibility and a near 100% case fatality rate. In over 10,000 cases, <20 instances of natural tumor regression have been detected. Previous work in this system has focused on Tasmanian devil genetic variation associated with the regression phenotype. Here, we used comparative and functional genomics to identify tumor genetic variation associated with tumor regression. We show that a single point mutation in the 5' untranslated region of the putative tumor suppressor RASL11A significantly contributes to tumor regression. RASL11A was expressed in regressed tumors but silenced in wild-type, nonregressed tumors, consistent with RASL11A downregulation in human cancers. Induced RASL11A expression significantly reduced tumor cell proliferation in vitro. The RAS pathway is frequently altered in human cancers, and RASL11A activation may provide a therapeutic treatment option for Tasmanian devils as well as a general mechanism for tumor inhibition.

Item Details

Item Type:Refereed Article
Keywords:Tasmanian devil, disease, genomics, DFTD, tumour, transmissible cancer, tumor regression, tumor suppressor, gene expression
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Genomics
Objective Division:Environmental Management
Objective Group:Terrestrial systems and management
Objective Field:Control of pests, diseases and exotic species in terrestrial environments
UTAS Author:Ruiz Aravena, M (Mr Manuel Ruiz Aravena)
UTAS Author:Hamede, R (Dr Rodrigo Hamede Ross)
UTAS Author:Jones, ME (Professor Menna Jones)
ID Code:142311
Year Published:2020
Web of Science® Times Cited:3
Deposited By:Zoology
Deposited On:2021-01-07
Last Modified:2021-01-08
Downloads:0

Repository Staff Only: item control page