RESEARCH ARTICLE


Characterization of Chromosomal Translocation Breakpoint Sequences in Solid Tumours: “An In Silico Analysis”



Aditi Daga 1, §, Afzal Ansari 2, §, Rakesh Rawal*, 3, Valentina Umrania 1
1 Department of Microbiology, MVM Science College, Saurashtra University, Rajkot, Gujarat, India
2 BIT Virtual Institute of Bioinformatics (GCRI Node), GSBTM, Gandhinagar, Gujarat, India
3 Department of Cancer Biology, The Gujarat Cancer & Research Institute, Ahmedabad, Gujarat, India


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© Daga et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Division of Medicinal Chemistry & Pharmacogenomics, Department of Cancer Biology, The Gujarat Cancer & Research Institute, NCH Campus, Asarwa, Ahmedabad-380016, Gujarat, India; Tel: 91-79-2268 8365; 8367; Fax: 91-79-22685490; Email: rakeshmrawal@gmail.com
§ These authors contributed equally in this research.


Abstract

Chromosomal translocations that results in formation and activation of fusion oncogenes are observed in numerous solid malignancies since years back. Expression of fusion kinases in these cancers drives the initiation & progression that ultimately leads to tumour development and thus comes out to be clinically imperative in terms of diagnosis and treatment of cancer. Nonetheless, molecular mechanisms beneath these translocations remained unexplored consequently limiting our knowledge of carcinogenesis and hence is the current field where further research is required. The issue of prime focus is the precision with which the chromosomes breaks and reunites within genome. Characterization of Genomic sequences located at Breakpoint region may direct us towards the thorough understanding of mechanism leading to chromosomal rearrangement. A unique computational multi-parametric analysis was performed for characterization of genomic sequence within and around breakpoint region. This study turns out to be novel as it reveals the occurrence of Segmental Duplications flanking the breakpoints of all translocation. Breakpoint Islands were also investigated for the presence of other intricate genomic architecture and various physico-chemical parameters. Our study particularly highlights the probable role of SDs and specific genomic features in precise chromosomal breakage. Additionally, it pinpoints the potential features that may be significant for double-strand breaks leading to chromosomal rearrangements.

Keywords: Breakpoint, chromosomal translocations, fusion protein, physico-chemical parameters, segmental duplication, solid tumours.