Abstract |
Rhabdoid tumors of early infancy are highly aggressive with consequent poor prognosis. Most cases show inactivation of the SMARCB1 (also known as INI1 and hSNF5) tumor suppressor, a core member of the ATP-dependent SWI/SNF chromatin-remodeling complex. Familial cases, described as rhabdoid tumor predisposition syndrome (RTPS), have been linked to heterozygous SMARCB1 germline mutations. We identified inactivation of another member of the SWI/SNF chromatin-remodeling complex, its ATPase subunit SMARCA4 (also known as BRG1), due to a SMARCA4/BRG1 germline mutation and loss of heterozygosity by uniparental disomy in the tumor cells of two sisters with rhabdoid tumors lacking SMARCB1 mutations. SMARCA4 is thus a second member of the SWI/SNF complex involved in cancer predisposition. Its general involvement in other tumor entities remains to be established.
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Authors | Reinhard Schneppenheim, Michael C Frühwald, Stefan Gesk, Martin Hasselblatt, Astrid Jeibmann, Uwe Kordes, Markus Kreuz, Ivo Leuschner, Jose Ignacio Martin Subero, Tobias Obser, Florian Oyen, Inga Vater, Reiner Siebert |
Journal | American journal of human genetics
(Am J Hum Genet)
Vol. 86
Issue 2
Pg. 279-84
(Feb 12 2010)
ISSN: 1537-6605 [Electronic] United States |
PMID | 20137775
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright (c) 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Codon, Nonsense
- Nuclear Proteins
- Transcription Factors
- SMARCA4 protein, human
- DNA Helicases
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Topics |
- Base Sequence
- Codon, Nonsense
(genetics)
- DNA Helicases
(chemistry, genetics)
- DNA Mutational Analysis
- Fatal Outcome
- Female
- Gene Silencing
- Genetic Predisposition to Disease
- Germ-Line Mutation
(genetics)
- Humans
- Immunohistochemistry
- Infant
- Magnetic Resonance Imaging
- Male
- Molecular Sequence Data
- Nuclear Proteins
(chemistry, genetics)
- Pedigree
- Rhabdoid Tumor
(genetics, pathology)
- Syndrome
- Transcription Factors
(chemistry, genetics)
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