title: The cellular etiology of chromosome translocations.
abstract: Chromosome translocations are the most severe form of genome defect. Translocations represent the end product of a series of cellular mistakes and they form after cells suffer multiple DNA double strand breaks (DSBs), which evade the surveillance mechanisms that usually eliminate them. Rather than being accurately repaired, translocating DSBs are misjoined to form aberrant fusion chromosomes. Although translocations have been extensively characterized using cytological methods and their pathological relevance in cancer and numerous other diseases is well established, how translocations form in the context of the intact cell nucleus is poorly understood. A combination of imaging approaches and biochemical methods to probe genome architecture and chromatin structure suggest that the spatial organization of the genome and features of chromatin, including sequence properties, higher order chromatin structure and histone modifications, are key determinants of translocation formation.
authors.affiliation: National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Roukos
authors.forename: Bharat
authors.initials: B
authors.lastname: Burman
authors.forename: Tom
authors.initials: T
authors.lastname: Misteli
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D055106:Genome-Wide Association Study; D006657:Histones / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D002843:Chromatin; D006657:Histones