دورية أكاديمية
أعرض في EDS

L1 retrotransposition is a common feature of mammalian hepatocarcinogenesis.

التفاصيل البيبلوغرافية
العنوان: L1 retrotransposition is a common feature of mammalian hepatocarcinogenesis.
المؤلفون: Schauer SN; Mater Research Institute-University of Queensland, Woolloongabba, QLD 4102, Australia., Carreira PE; Mater Research Institute-University of Queensland, Woolloongabba, QLD 4102, Australia., Shukla R; Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE1 7RU, United Kingdom., Gerhardt DJ; Mater Research Institute-University of Queensland, Woolloongabba, QLD 4102, Australia.; Invenra, Incorporated, Madison, Wisconsin 53719, USA., Gerdes P; Mater Research Institute-University of Queensland, Woolloongabba, QLD 4102, Australia., Sanchez-Luque FJ; Mater Research Institute-University of Queensland, Woolloongabba, QLD 4102, Australia.; Department of Genomic Medicine, GENYO, Centre for Genomics and Oncological Research: Pfizer-University of Granada-Andalusian Regional Government, PTS Granada, 18016 Granada, Spain., Nicoli P; Department of Experimental Oncology, European Institute of Oncology, 20146 Milan, Italy., Kindlova M; Mater Research Institute-University of Queensland, Woolloongabba, QLD 4102, Australia., Ghisletti S; Humanitas Clinical and Research Center, 20089 Milan, Italy., Santos AD; INSERM, U1193, Paul-Brousse University Hospital, Hepatobiliary Centre, Villejuif 94800, France.; Université Paris-Sud, Faculté de Médecine, Villejuif 94800, France., Rapoud D; INSERM, U1193, Paul-Brousse University Hospital, Hepatobiliary Centre, Villejuif 94800, France.; Université Paris-Sud, Faculté de Médecine, Villejuif 94800, France., Samuel D; INSERM, U1193, Paul-Brousse University Hospital, Hepatobiliary Centre, Villejuif 94800, France.; Université Paris-Sud, Faculté de Médecine, Villejuif 94800, France., Faivre J; INSERM, U1193, Paul-Brousse University Hospital, Hepatobiliary Centre, Villejuif 94800, France.; Université Paris-Sud, Faculté de Médecine, Villejuif 94800, France.; Assistance Publique-Hôpitaux de Paris (AP-HP), Pôle de Biologie Médicale, Paul-Brousse University Hospital, Villejuif 94800, France., Ewing AD; Mater Research Institute-University of Queensland, Woolloongabba, QLD 4102, Australia., Richardson SR; Mater Research Institute-University of Queensland, Woolloongabba, QLD 4102, Australia., Faulkner GJ; Mater Research Institute-University of Queensland, Woolloongabba, QLD 4102, Australia.; School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia.; Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia.
المصدر: Genome research [Genome Res] 2018 May; Vol. 28 (5), pp. 639-653. Date of Electronic Publication: 2018 Apr 11.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cold Spring Harbor Laboratory Press Country of Publication: United States NLM ID: 9518021 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1549-5469 (Electronic) Linking ISSN: 10889051 NLM ISO Abbreviation: Genome Res Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cold Spring Harbor, N.Y. : Cold Spring Harbor Laboratory Press, c1995-
مواضيع طبية MeSH: Carcinoma, Hepatocellular/*genetics , Liver Neoplasms/*genetics , Long Interspersed Nucleotide Elements/*genetics , Retroelements/*genetics, ATP Binding Cassette Transporter, Subfamily B/genetics ; Adult ; Aged ; Aged, 80 and over ; Animals ; Cell Transformation, Neoplastic/genetics ; Female ; Humans ; Liver/metabolism ; Liver/pathology ; Male ; Mammals/genetics ; Mice, Knockout ; Middle Aged ; Mutagenesis, Insertional ; ATP-Binding Cassette Sub-Family B Member 4
مستخلص: The retrotransposon Long Interspersed Element 1 (LINE-1 or L1) is a continuing source of germline and somatic mutagenesis in mammals. Deregulated L1 activity is a hallmark of cancer, and L1 mutagenesis has been described in numerous human malignancies. We previously employed retrotransposon capture sequencing (RC-seq) to analyze hepatocellular carcinoma (HCC) samples from patients infected with hepatitis B or hepatitis C virus and identified L1 variants responsible for activating oncogenic pathways. Here, we have applied RC-seq and whole-genome sequencing (WGS) to an Abcb4 (Mdr2) -/- mouse model of hepatic carcinogenesis and demonstrated for the first time that L1 mobilization occurs in murine tumors. In 12 HCC nodules obtained from 10 animals, we validated four somatic L1 insertions by PCR and capillary sequencing, including T F subfamily elements, and one G F subfamily example. One of the T F insertions carried a 3' transduction, allowing us to identify its donor L1 and to demonstrate that this full-length T F element retained retrotransposition capacity in cultured cancer cells. Using RC-seq, we also identified eight tumor-specific L1 insertions from 25 HCC patients with a history of alcohol abuse. Finally, we used RC-seq and WGS to identify three tumor-specific L1 insertions among 10 intra-hepatic cholangiocarcinoma (ICC) patients, including one insertion traced to a donor L1 on Chromosome 22 known to be highly active in other cancers. This study reveals L1 mobilization as a common feature of hepatocarcinogenesis in mammals, demonstrating that the phenomenon is not restricted to human viral HCC etiologies and is encountered in murine liver tumors.
(© 2018 Schauer et al.; Published by Cold Spring Harbor Laboratory Press.)
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المشرفين على المادة: 0 (ATP Binding Cassette Transporter, Subfamily B)
0 (Retroelements)
تواريخ الأحداث: Date Created: 20180413 Date Completed: 20181011 Latest Revision: 20231213
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5932605
DOI: 10.1101/gr.226993.117
PMID: 29643204
قاعدة البيانات: MEDLINE
الوصف
تدمد:1549-5469
DOI:10.1101/gr.226993.117