Table of Contents
ISRN Genomics
Volume 2013 (2013), Article ID 921418, 18 pages
Review Article

Critical Analysis of Strand-Biased Somatic Mutation Signatures in TP53 versus Ig Genes, in Genome-Wide Data and the Etiology of Cancer

1Melville Analytics Pty. Ltd., Unit 14, Nuggets Crossing, Jindabyne, NSW 2627, Australia
2School of Veterinary and Biomedical Sciences, Murdoch University, South Street, Murdoch, WA 6150, Australia

Received 4 September 2012; Accepted 23 October 2012

Academic Editors: S. N. Shchelkunov and A. Stubbs

Copyright © 2013 Robyn A. Lindley and Edward J. Steele. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Previous analyses of rearranged immunoglobulin (Ig) variable genes (VDJs) concluded that the mechanism of Ig somatic hypermutation (SHM) involves the Ig pre-mRNA acting as a copying template resulting in characteristic strand biased somatic mutation patterns at A:T and G:C base pairs. We have since analysed cancer genome data and found the same mutation strand-biases, in toto or in part, in nonlymphoid cancers. Here we have analysed somatic mutations in a single well-characterised gene TP53. Our goal is to understand the genesis of the strand-biased mutation patterns in TP53—and in genome-wide data—that may arise by “endogenous” mechanisms as opposed to adduct-generated DNA-targeted strand-biased mutations caused by well-characterised “external” carcinogenic influences in cigarette smoke, UV-light, and certain dietary components. The underlying strand-biased mutation signatures in TP53, for many non-lymphoid cancers, bear a striking resemblance to the Ig SHM pattern. A similar pattern can be found in genome-wide somatic mutations in cancer genomes that have also mutated TP53. The analysis implies a role for base-modified RNA template intermediates coupled to reverse transcription in the genesis of many cancers. Thus Ig SHM may be inappropriately activated in many non-lymphoid tissues via hormonal and/or inflammation-related processes leading to cancer.