The mammalian nucleus is a highly complex structure that carries out a diverse 
range of functions such as DNA replication, cell division, RNA processing, and 
nuclear export/import. Many of these activities occur at discrete 
subcompartments that intersect with specific regions of the genome. Over the 
past few decades, evidence has accumulated to suggest that RNA transcription 
also occurs in specialized sites, called transcription factories, that may 
influence how the genome is organized. There may be certain efficiency benefits 
to cluster transcriptional activity in this way. However, the clustering of 
genes at transcription factories may have consequences for genome stability, and 
increase the susceptibility to recurrent chromosomal translocations that lead to 
cancer. The relationships between genome organization, transcription, and 
chromosomal translocation formation will have important implications in 
understanding the causes of therapy-related cancers.