Significant Role of Segmental Duplications and SIDD Sites in Chromosomal Translocations of Hematological Malignancies: A Multi-parametric Bioinformatic Analysis.

ABSTRACT

Recurrent non-random chromosomal translocations are hallmark characteristics of leukemogenesis, and however, molecular mechanisms underlying these rearrangements are less explored. The fundamental question is, why and how chromosomes break and reunite so precisely in the genome. Meticulous understanding of mechanism leading to chromosomal rearrangement can be achieved by characterizing breakpoints. To address this hypothesis, a novel multi-parametric computational approach for characterization of major leukemic translocations within and around breakpoint region was performed. To best of our knowledge, this bioinformatic analysis is unique in finding the presence of segmental duplications (SDs) flanking breakpoints of all major leukemic translocation. Breakpoint islands (BpIs) were analyzed for stress-induced duplex destabilization (SIDD) sites along with other complex genomic architecture and physicochemical properties. Our study distinctly emphasizes on the probable correlative role of SDs, SIDD sites and various genomic features in the occurrence of breakpoints. Further, it also highlights potential features which may be playing a crucial role in causing double-strand breaks, leading to translocation.