Human PGBD5 DNA transposase promotes site-specific oncogenic mutations in rhabdoid tumors
نویسندگان
چکیده
Anton G. Henssen, Richard Koche, Jiali Zhuang, Eileen Jiang, Casie Reed, Amy 4 Eisenberg, Eric Still, Ian C. MacArthur, Elias Rodríguez-Fos, Santiago Gonzalez, Montserrat 5 Puiggròs, Andrew N. Blackford, Christopher E. Mason, Elisa de Stanchina, Mithat Gönen, 6 Anne-Katrin Emde, Minita Shah, Kanika Arora, Catherine Reeves, Nicholas D. Socci, 7 Elizabeth Perlman, Cristina R. Antonescu, Charles W. M. Roberts, Hanno Steen, 8 Elizabeth Mullen, Stephen P. Jackson, David Torrents, Zhiping Weng, Scott A. 9 Armstrong, and Alex Kentsis * 10
منابع مشابه
Therapeutic targeting of PGBD5-induced DNA repair dependency in pediatric solid tumors.
Despite intense efforts, the cure rates of childhood and adult solid tumors are not satisfactory. Resistance to intensive chemotherapy is common, and targets for molecular therapies are largely undefined. We have found that the majority of childhood solid tumors, including rhabdoid tumors, neuroblastoma, medulloblastoma, and Ewing sarcoma, express an active DNA transposase, PGBD5, that can prom...
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Transposons are mobile genetic elements that are found in nearly all organisms, including humans. Mobilization of DNA transposons by transposase enzymes can cause genomic rearrangements, but our knowledge of human genes derived from transposases is limited. In this study, we find that the protein encoded by human PGBD5, the most evolutionarily conserved transposable element-derived gene in vert...
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Germ-line and acquired mutations of the hSNF5/INI1 tumor suppressor gene have been reported in central nervous system (CNS), renal, and soft-tissue rhabdoid tumors. The present study was designed to compare the types of INI1 alterations among tumors from diverse anatomical sites and identify mutation hot spots. Fluorescence in situ hybridization and PCR-based microsatellite, heteroduplex, and s...
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Rhabdoid tumor of the kidney is a rare and aggressive childhood cancer (1). Although the infant kidney is the most common site of rhabdoid tumors, these tumors occasionally occur at other sites and in older children and adults (2,3). Less than 25% of infants and young children with rhabdoid tumor of the kidney survive (4,5). Rhabdoid tumor is defined histologically by large cells, which may res...
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We examined 18 atypical teratoid and rhabdoid tumors of the brain and 7 renal and 4 extrarenal rhabdoid tumors for mutations in the candidate rhabdoid tumor suppressor gene, INI1. Fifteen tumors had homozygous deletions of one or more exons of the INI1 gene, and the other 14 tumors demonstrated mutations. Germ-line mutations of INI1 were identified in four children, one with an atypical teratoi...
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