File(s) under permanent embargo
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, ASpontaneous 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.
Funding
National Institutes of Health
History
Publication title
GeneticsVolume
215Issue
4Pagination
1143-1152ISSN
1943-2631Department/School
School of Natural SciencesPublisher
Oxford University PressPlace of publication
United StatesRights statement
Copyright © 2020 by the Genetics Society of AmericaRepository Status
- Restricted