Human PGBD5 DNA transposase promotes site-specific oncogenic mutations in rhabdoid tumors
作者： Nicholas D. Socci , Richard Koche , Elisa de Stanchina , Amy Eisenberg , Kanika Arora
DOI: 10.1101/111138
关键词:
摘要: Genomic rearrangements are a hallmark of childhood solid tumors, but their mutational causes remain poorly understood. Here, we identify the piggyBac transposable element derived 5 (PGBD5) gene as an enzymatically active human DNA transposase expressed in majority rhabdoid lethal cancer. Using assembly-based whole-genome sequencing, observed previously unknown somatic genomic primary tumors. These were characterized by deletions and inversions involving PGBD5-specific signal (PSS) sequences at breakpoints, with some recurrently targeting tumor suppressor genes, leading to inactivation. PGBD5 was found be physically associated PSS that also sufficient mediate PGBD5-induced cells. We ectopic expression immortalized cells promote penetrant cell transformation vitro immunodeficient mice vivo. This activity required specific catalytic residues domain, well end-joining repair, induced distinct structural rearrangements, PSS-associated similar those defines oncogenic mutator provides plausible mechanism for site adult
sci-hub.st 参考文章(43)
H.-P. Fischer, H. Thomsen, M. Altmannsberger, U. Bertram, Malignant rhabdoid tumour of the kidney expressing neurofilament proteins. Immunohistochemical findings and histogenetic aspects. Pathology Research and Practice. ,vol. 184, pp. 541- 547 ,(1989) , 10.1016/S0344-0338(89)80149-9
Nemanja Rodić, Jared P Steranka, Alvin Makohon-Moore, Allison Moyer, Peilin Shen, Reema Sharma, Zachary A Kohutek, Cheng Ran Huang, Daniel Ahn, Paolo Mita, Martin S Taylor, Norman J Barker, Ralph H Hruban, Christine A Iacobuzio-Donahue, Jef D Boeke, Kathleen H Burns, Retrotransposon insertions in the clonal evolution of pancreatic ductal adenocarcinoma Nature Medicine. ,vol. 21, pp. 1060- 1064 ,(2015) , 10.1038/NM.3919
William C. Hahn, Christopher M. Counter, Ante S. Lundberg, Roderick L. Beijersbergen, Mary W. Brooks, Robert A. Weinberg, Creation of human tumour cells with defined genetic elements Nature. ,vol. 400, pp. 464- 468 ,(1999) , 10.1038/22780
Elli Papaemmanuil, Inmaculada Rapado, Yilong Li, Nicola E Potter, David C Wedge, Jose Tubio, Ludmil B Alexandrov, Peter Van Loo, Susanna L Cooke, John Marshall, Inigo Martincorena, Jonathan Hinton, Gunes Gundem, Frederik W van Delft, Serena Nik-Zainal, David R Jones, Manasa Ramakrishna, Ian Titley, Lucy Stebbings, Catherine Leroy, Andrew Menzies, John Gamble, Ben Robinson, Laura Mudie, Keiran Raine, Sarah O'Meara, Jon W Teague, Adam P Butler, Giovanni Cazzaniga, Andrea Biondi, Jan Zuna, Helena Kempski, Markus Muschen, Anthony M Ford, Michael R Stratton, Mel Greaves, Peter J Campbell, RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia Nature Genetics. ,vol. 46, pp. 116- 125 ,(2014) , 10.1038/NG.2874
Eitan Halper-Stromberg, Jared Steranka, Nicolas Giraldo-Castillo, Timothy Fuller, Stephen Desiderio, Kathleen H Burns, Fine mapping of V(D)J recombinase mediated rearrangements in human lymphoid malignancies BMC Genomics. ,vol. 14, pp. 565- 565 ,(2013) , 10.1186/1471-2164-14-565
Robert Huether, Li Dong, Xiang Chen, Gang Wu, Matthew Parker, Lei Wei, Jing Ma, Michael N Edmonson, Erin K Hedlund, Michael C Rusch, Sheila A Shurtleff, Heather L Mulder, Kristy Boggs, Bhavin Vadordaria, Jinjun Cheng, Donald Yergeau, Guangchun Song, Jared Becksfort, Gordon Lemmon, Catherine Weber, Zhongling Cai, Jinjun Dang, Michael Walsh, Amanda L Gedman, Zachary Faber, John Easton, Tanja Gruber, Richard W Kriwacki, Janet F Partridge, Li Ding, Richard K Wilson, Elaine R Mardis, Charles G Mullighan, Richard J Gilbertson, Suzanne J Baker, Gerard Zambetti, David W Ellison, Jinghui Zhang, James R Downing, None, The landscape of somatic mutations in epigenetic regulators across 1,000 paediatric cancer genomes Nature Communications. ,vol. 5, pp. 3630- 3630 ,(2014) , 10.1038/NCOMMS4630
C. Marcelo Aldaz, Brent W. Ferguson, Martin C. Abba, WWOX at the crossroads of cancer, metabolic syndrome related traits and CNS pathologies Biochimica et Biophysica Acta. ,vol. 1846, pp. 188- 200 ,(2014) , 10.1016/J.BBCAN.2014.06.001
Marry M. van den Heuvel-Eibrink, Harm van Tinteren, Harriet Rehorst, Aurore Coulombe, Catharine Patte, Beatriz de Camargo, Jan de Kraker, Ivo Leuschner, Rieneke Lugtenberg, Kathy Pritchard-Jones, Bengt Sandstedt, Filippo Spreafico, Norbert Graf, Gordan M. Vujanic, Malignant rhabdoid tumours of the kidney (MRTKs), registered on recent SIOP protocols from 1993 to 2005: a report of the SIOP renal tumour study group. Pediatric Blood & Cancer. ,vol. 56, pp. 733- 737 ,(2011) , 10.1002/PBC.22922
S. Majumdar, A. Singh, D. C. Rio, The Human THAP9 Gene Encodes an Active P-Element DNA Transposase Science. ,vol. 339, pp. 446- 448 ,(2013) , 10.1126/SCIENCE.1231789
Valentí Moncunill, Santi Gonzalez, Sílvia Beà, Lise O Andrieux, Itziar Salaverria, Cristina Royo, Laura Martinez, Montserrat Puiggròs, Maia Segura-Wang, Adrian M Stütz, Alba Navarro, Romina Royo, Josep L Gelpí, Ivo G Gut, Carlos López-Otín, Modesto Orozco, Jan O Korbel, Elias Campo, Xose S Puente, David Torrents, None, Comprehensive characterization of complex structural variations in cancer by directly comparing genome sequence reads Nature Biotechnology. ,vol. 32, pp. 1106- 1112 ,(2014) , 10.1038/NBT.3027