Modelling Mutation Spectra of Human Carcinogens Using Experimental Systems.

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Modelling Mutation Spectra of Human Carcinogens Using Experimental Systems.

Basic Clin Pharmacol Toxicol. 2017 Sep;121 Suppl 3:16-22

Authors: Zhivagui M, Korenjak M, Zavadil J

Abstract
Mutation spectra in cancer genomes provide information on the disease aetiology and the causality underlying the evolution and progression of cancer. Genome-wide mutation patterns reflect the effects of mutagenic insults and can thus reveal past carcinogen-specific exposures and inform hypotheses on the causative factors for specific cancer types. To identify mutation profiles in human cancers, single-gene studies were first employed, focusing mainly on the tumour suppressor gene TP53. Furthermore, experimental studies had been developed in model organisms. They allowed the characterization of the mutation patterns specific to known human carcinogens, such as polycyclic aromatic hydrocarbons or ultraviolet light. With the advent of massively parallel sequencing, mutation landscapes become revealed on a large scale, in human primary tumours and in experimental models, enabling deeper investigations of the functional and structural impact of mutations on the genome, including exposure-specific base-change fingerprints known as mutational signatures. These studies can now accelerate the identification of aetiological factors, contribute to carcinogen evaluation and classification and ultimately inform cancer prevention measures.

PMID: 27754614 [PubMed – indexed for MEDLINE]

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