Making of fusion genes in cancer: An in-silico study of mechanism of chromosomal translocations

Abstract

Chromosomal translocations involve exchange of genetic material between nonhomologous 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.PeerJ Preprints | https://doi.org/10.7287/peerj.preprints.26571v1 | CC BY 4.0 Open Access | rec: