دورية أكاديمية

Spontaneous Tumor Regression in Tasmanian Devils Associated with RASL11A Activation.

التفاصيل البيبلوغرافية
العنوان: Spontaneous Tumor Regression in Tasmanian Devils Associated with RASL11A Activation.
المؤلفون: Margres MJ; School of Biological Sciences, Washington State University, Pullman, Washington 99164 mark_margres@fas.harvard.edu.; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138., Ruiz-Aravena M; School of Natural Sciences, University of Tasmania, Hobart, Tasmania 7001, Australia., Hamede R; School of Natural Sciences, University of Tasmania, Hobart, Tasmania 7001, Australia.; Centre for Integrative Ecology, Deakin University, Waurn Ponds, Victoria 3216, Australia., Chawla K; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109.; Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109., Patton AH; School of Biological Sciences, Washington State University, Pullman, Washington 99164., Lawrance MF; School of Biological Sciences, Washington State University, Pullman, Washington 99164., Fraik AK; School of Biological Sciences, Washington State University, Pullman, Washington 99164., Stahlke AR; Department of Biological Sciences, Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, Idaho 83844., Davis BW; Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas 77843.; Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892., Ostrander EA; Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892., Jones ME; School of Natural Sciences, University of Tasmania, Hobart, Tasmania 7001, Australia., McCallum H; School of Environment, Griffith University, Nathan, Queensland 4111, Australia., Paddison PJ; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109., Hohenlohe PA; Department of Biological Sciences, Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, Idaho 83844., Hockenbery D; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109.; Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109., Storfer A; School of Biological Sciences, Washington State University, Pullman, Washington 99164.
المصدر: Genetics [Genetics] 2020 Aug; Vol. 215 (4), pp. 1143-1152. Date of Electronic Publication: 2020 Jun 18.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: United States NLM ID: 0374636 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1943-2631 (Electronic) Linking ISSN: 00166731 NLM ISO Abbreviation: Genetics Subsets: MEDLINE
أسماء مطبوعة: Publication: 2021- : [Oxford] : Oxford University Press
Original Publication: Austin, Tex. [etc.]
مواضيع طبية MeSH: Cell Proliferation* , Gene Expression Regulation, Neoplastic* , Neoplasm Regression, Spontaneous*, Marsupialia/*physiology , Monomeric GTP-Binding Proteins/*metabolism , Neoplasms/*veterinary, Animals ; Female ; Monomeric GTP-Binding Proteins/genetics ; Neoplasms/genetics ; Neoplasms/pathology ; Tumor Cells, Cultured
مستخلص: 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.
(Copyright © 2020 by the Genetics Society of America.)
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معلومات مُعتمدة: P30 GM103324 United States GM NIGMS NIH HHS; R01 GM126563 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: cancer; gene expression; tumor regression; tumor suppressor
المشرفين على المادة: EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
تواريخ الأحداث: Date Created: 20200620 Date Completed: 20210706 Latest Revision: 20210802
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7404226
DOI: 10.1534/genetics.120.303428
PMID: 32554701
قاعدة البيانات: MEDLINE
الوصف
تدمد:1943-2631
DOI:10.1534/genetics.120.303428