Highly penetrant, rapid tumorigenesis through conditional inversion of the tumor suppressor gene Snf5.
Recent data suggest the SWI/SNF chromatin remodeling complex may also act as a tumor suppressor. Utilizing a reversibly inactivating conditional allele, we demonstrate that loss of Snf5/Ini1/Baf47/SmarcB1, a core subunit of SWI/SNF, results in highly penetrant cancer predisposition with 100% of mice developing mature CD8(+) T cell lymphoma or rare rhabdoid tumors with a median onset of only 11 weeks. Notably, while loss of Snf5 predisposes to aggressive cancers, it is also required for survival of virtually all nonmalignant cells in vivo. Reversible gene targeting demonstrates a critical and specific role for Snf5 in tumor suppression, provides a novel system in which to explore the genetic pathways involved in tumor suppression by Swi/Snf, and should be of wide use in evaluating other essential tumor suppressor genes.
Roberts
Charles W M
CW
Division of Hematology-Oncology, Dana-Farber Cancer Institute and Children's Hospital, Department of Pediatrics, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA.
Leroux
Monique M
MM
Fleming
Mark D
MD
Orkin
Stuart H
SH
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002868:Chromosomal Proteins, Non-Histone; D007446:Chromosome Inversion; D004268:DNA-Binding Proteins / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D019683:Penetrance; D018335:Rhabdoid Tumor / Q000235:genetics*; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000235:genetics*
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513265:Smarcb1 protein, mouse; D014157:Transcription Factors