Translocation and deletion breakpoints in cancer genomes are associated with potential non-B DNA-forming sequences.

摘要: Gross chromosomal rearrangements (including translocations, deletions, insertions and duplications) are a hallmark of cancer genomes often create oncogenic fusion genes. An obligate step in the generation such gross is formation DNA double-strand breaks (DSBs). Since genomic distribution rearrangement breakpoints non-random, intrinsic cellular factors may predispose certain regions to breakage. Notably, sequences with potential fold into secondary structures [potential non-B (PONDS); e.g. triplexes, quadruplexes, hairpin/cruciforms, Z-DNA single-stranded looped-out implications replication transcription] can stimulate DSBs. Here, we tested postulate that these might be found at, or close proximity to, breakpoints. By analyzing PONDS-forming within ±500 bases 19 947 translocation 46 365 sequence-characterized deletion genomes, find significant association between repeats Specifically, (AT)n, (GAA)n (GAAA)n constitute most frequent at breakpoints, whereas A-tracts occur preferentially Translocation near also recur different individuals patient tumor samples. Hence, represent an risk factor for genomes.