Genetic exchange between chromosomes can cause cells to become cancerous. Most cases of<unk><unk>  (about 85%) are the result of a defining genetic event; a reciprocal translocation between chromosomes 11 and 22, t(11,22), which fuses the<unk>  Breakpoint Region 1 <unk> R1) gene of chromosome 22 (which encodes the<unk>  protein) to the Friend Leukemia Virus Integration 1 (FLI1) gene (which encodes Friend Leukemia Integration 1 transcription factor (FLI1), a member of the ETS transcription factor family) of chromosome 11. The resultant chromosomal translocation causes the<unk>  trans-activation domain (which is usually silent in the wild type) to become very active, this leads to the translation of a new<unk> -FLI1 fusion protein.<unk>  proteins are involved in meiosis, B-lymphocyte maturation, hematopoietic stem cell renewal, DNA repair and cell senescence. ETS transcription factors are involved in cell differentiation and cell cycle control. The<unk> -FLI1 fusion protein has phase transition properties, allowing it to transition into liquid-like, phase separated compartments consisting of membrane-less organelles. This phase transition property allows the fusion protein to access and activate micro-satellite regions of the genome that would otherwise be inaccessible. This fusion protein can convert usually silent chromatin regions into fully active enhancers leading to oncogenesis of the cells. The<unk> -FLI1 fusion protein also causes variable expression of the genome via epigenetic mechanisms. The fusion protein does this by recruiting enzymes that affect DNA methylation, histone acetylation and direct inhibition of non-coding microRNA.<unk> -FLI1 promotes histone acetylation, which leads to uncoiling of DNA (which is usually tightly wound around histones); this chromatin relaxation leads to the DNA being more accessible to transcription factors and thus enhancing the expression of the associated genes. DNA methylation leads to gene silencing as it prevents transcription factor binding.<unk> -FLI1 reduces DNA methylation (which occurs mostly in areas corresponding to transcription enhancers), leading to increased gene expression. The<unk> -FLI1 fusion protein inhibits certain microRNAs of cells (such as miRNA-145). MiRNA-145 normally activates RNA-induced silencing complexes (RISCs) to inhibit or degrade mRNA that is involved in cell pluripotency. Thus,<unk> W-FLI1 inhibition of the microRNA miRNA-145 leads to increased pluripotency and decreased differentiation of cells and increased oncogenesis. A genome-wide association study (GWAS) identified three susceptibility loci located on chromosomes 1, 10 and 15. A continuative study discovered that the<unk><unk>  susceptibility gene EGR2, which is located within the chromosome 10 susceptibility locus, is regulated by the<unk> R1-FLI1 fusion oncogene via a GGAA-microsatellite.<unk> /FLI functions as the master regulator. Other translocations are at t(21;22) and t(7;22).<unk><unk>  cells are positive for CD99 and MIC2, and negative for CD45.
Ewing's sarcoma
Osteosarcoma
Osteoblastoma
Eosinophilic granuloma
Enchondroma
Neuroblastoma
Synovial sarcoma
Osteomyelitis