Making of fusion genes in cancer: An in-silico study of mechanism of chromosomal translocations
- Published
- Accepted
- Subject Areas
- Bioinformatics, Computational Biology
- Keywords
- instability of DNA, Chromosomal translocations, carcinogenesis, in-silico approach, physico-chemical properties, prone to breakage, fusion sequences, gene expression
- Copyright
- © 2018 Lalwani et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
- Cite this article
- 2018. Making of fusion genes in cancer: An in-silico study of mechanism of chromosomal translocations. PeerJ Preprints 6:e26571v1 https://doi.org/10.7287/peerj.preprints.26571v1
Abstract
Chromosomal translocations involve exchange of genetic material between non- homologous chromosomes leading to the formation of a fusion gene with altered function. The clinical consequences of non-random and recurrent chromosomal translocations have been so well understood in carcinogenesis that they serve as diagnostic and prognostic markers and also help in therapy decisions, mainly in leukemia and lymphoma. However, the molecular mechanisms underlying these recurrent genetic exchanges are yet to be understood. Various approaches employed include the extent of the vicinity of the partner chromosomes in the nucleus, DNA sequences at the breakpoints, etc. The present study addresses the stability of DNA sequences at the breakpoint regions using in-silico approach in terms of physicochemical properties such as; AT%, flexibility, melting temperature, enthalpy, entropy, stacking energy and free energy. Changes in these properties may lead to instability of DNA which could affect gene expression in particular and genome organization in general. Our study indicates that the fusion sequences are comparatively more unstable and hence, more prone to breakage. Current study along with others could lead to developing a model for predicting breakage prone genomic regions using this novel in-silico approach.
Author Comment
This is a submission to PeerJ Computer Science for review.
Supplemental Information
Supplementary tables showing Data retrieval using TICdb and analysis of physico-chemical properties of fusion sequences and respective controls using DiProGb software
Tables 1-4 show the nucleotide sequence of fusion partners retrieved from TICdb for all four fusion pairs i.e. BCR/ABL, PML/RARA, AML/ETO, and CBFB/MYH11.
Tables 5-8 show analysis of physico-chemical parameters/AT% of fusion sequences (100 &1000 bp upstream and downstream FS) for all four fusion pairs.
Tables 9-16 show analysis of physico-chemical parameters/AT% of control sequences (100 &1000 bp upstream and downstream FS).