SWI/SNF chromatin remodeling and human malignancies.
The SWI/SNF complexes, initially identified in yeast 20 years ago, are a family of multi-subunit complexes that use the energy of adenosine triphosphate (ATP) hydrolysis to remodel nucleosomes. Chromatin remodeling processes mediated by the SWI/SNF complexes are critical to the modulation of gene expression across a variety of cellular processes, including stemness, differentiation, and proliferation. The first evidence of the involvement of these complexes in carcinogenesis was provided by the identification of biallelic, truncating mutations of the SMARCB1 gene in malignant rhabdoid tumors, a highly aggressive childhood cancer. Subsequently, genome-wide sequencing technologies have identified mutations in genes encoding different subunits of the SWI/SNF complexes in a large number of tumors. SWI/SNF mutations, and the subsequent abnormal function of SWI/SNF complexes, are among the most frequent gene alterations in cancer. The mechanisms by which perturbation of the SWI/SNF complexes promote oncogenesis are not fully elucidated; however, alterations of SWI/SNF genes obviously play a major part in cancer development, progression, and/or resistance to therapy.
Unité de Génétique Somatique.
Julien
J
Masliah-Planchon
Ivan
I
Bièche
Jean-Marc
JM
Guinebretière
Franck
F
Bourdeaut
Olivier
O
Delattre
D000818:Animals; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors
cancer; epigenetic; nucleosome; remodeling; transcription