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Journal article
Critical analysis of strand-biased somatic mutation signatures in TP53 versus Ig genes, in genome-wide data and the etiology of cancer
2012 International Conference on Computer & Information Science (ICCIS), Vol.2013, Article ID 921418
2012
Abstract
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 nonlymphoid 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.
Details
- Title
- Critical analysis of strand-biased somatic mutation signatures in TP53 versus Ig genes, in genome-wide data and the etiology of cancer
- Authors/Creators
- R.A. Lindley (Author/Creator)E.J. Steele (Author/Creator)
- Publication Details
- 2012 International Conference on Computer & Information Science (ICCIS), Vol.2013, Article ID 921418
- Identifiers
- 991005542523807891
- Copyright
- © The Authors 2012. Creative Commons Attribution license
- Murdoch Affiliation
- School of Veterinary and Biomedical Sciences
- Language
- English
- Resource Type
- Journal article
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