دورية أكاديمية
أعرض في EDS

A single-copy Sleeping Beauty transposon mutagenesis screen identifies new PTEN-cooperating tumor suppressor genes.

التفاصيل البيبلوغرافية
العنوان: A single-copy Sleeping Beauty transposon mutagenesis screen identifies new PTEN-cooperating tumor suppressor genes.
المؤلفون: de la Rosa J; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.; Instituto de Medicina Oncológica y Molecular de Asturias (IMOMA), Oviedo, Spain.; Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, Oviedo, Spain., Weber J; Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, München, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Friedrich MJ; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK., Li Y; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK., Rad L; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK., Ponstingl H; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK., Liang Q; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK., de Quirós SB; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK., Noorani I; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK., Metzakopian E; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK., Strong A; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK., Li MA; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK., Astudillo A; Servicio de Anatomía Patológica, Hospital Universitario Central de Asturias, Oviedo, Spain., Fernández-García MT; Unidad de Histopatología Molecular, Facultad de Medicina, IUOPA, Universidad de Oviedo, Oviedo, Spain., Fernández-García MS; Unidad de Histopatología Molecular, Facultad de Medicina, IUOPA, Universidad de Oviedo, Oviedo, Spain., Hoffman GJ; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.; School of Medicine, University of Western Australia, Crawley, Western Australia, Australia., Fuente R; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK., Vassiliou GS; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK., Rad R; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.; Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, München, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., López-Otín C; Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, Oviedo, Spain.; Centro de Investigación Biomédica en Red de Cáncer, Spain., Bradley A; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK., Cadiñanos J; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.; Instituto de Medicina Oncológica y Molecular de Asturias (IMOMA), Oviedo, Spain.
المصدر: Nature genetics [Nat Genet] 2017 May; Vol. 49 (5), pp. 730-741. Date of Electronic Publication: 2017 Mar 20.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Co Country of Publication: United States NLM ID: 9216904 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1718 (Electronic) Linking ISSN: 10614036 NLM ISO Abbreviation: Nat Genet Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Nature Pub. Co., c1992-
مواضيع طبية MeSH: Genes, Tumor Suppressor* , Mutagenesis, Insertional*, DNA Transposable Elements/*genetics , PTEN Phosphohydrolase/*genetics , Prostatic Neoplasms/*genetics, Animals ; Cell Line ; Cell Movement/genetics ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Gene Dosage ; Genetic Predisposition to Disease/genetics ; Humans ; Kaplan-Meier Estimate ; Male ; Mice, Knockout ; Mice, Transgenic ; Mutation ; Prostate/cytology ; Prostate/metabolism ; RNA Interference ; Signal Transduction/genetics
مستخلص: The overwhelming number of genetic alterations identified through cancer genome sequencing requires complementary approaches to interpret their significance and interactions. Here we developed a novel whole-body insertional mutagenesis screen in mice, which was designed for the discovery of Pten-cooperating tumor suppressors. Toward this aim, we coupled mobilization of a single-copy inactivating Sleeping Beauty transposon to Pten disruption within the same genome. The analysis of 278 transposition-induced prostate, breast and skin tumors detected tissue-specific and shared data sets of known and candidate genes involved in cancer. We validated ZBTB20, CELF2, PARD3, AKAP13 and WAC, which were identified by our screens in multiple cancer types, as new tumor suppressor genes in prostate cancer. We demonstrated their synergy with PTEN in preventing invasion in vitro and confirmed their clinical relevance. Further characterization of Wac in vivo showed obligate haploinsufficiency for this gene (which encodes an autophagy-regulating factor) in a Pten-deficient context. Our study identified complex PTEN-cooperating tumor suppressor networks in different cancer types, with potential clinical implications.
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معلومات مُعتمدة: United Kingdom Wellcome Trust; MC_PC_12009 United Kingdom MRC_ Medical Research Council
المشرفين على المادة: 0 (DNA Transposable Elements)
EC 3.1.3.67 (PTEN Phosphohydrolase)
EC 3.1.3.67 (Pten protein, mouse)
تواريخ الأحداث: Date Created: 20170321 Date Completed: 20170918 Latest Revision: 20220129
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5409503
DOI: 10.1038/ng.3817
PMID: 28319090
قاعدة البيانات: MEDLINE
الوصف
تدمد:1546-1718
DOI:10.1038/ng.3817