Characterization of mutational signatures in human cancer cell lines reveals episodic APOBEC mutagenesis

Dataset ID Technology Samples
EGAD00001004203 HiSeq X Ten 192

Dataset Description

Multiple signatures of somatic mutations have been identified in human cancer genomes. To investigate whether mutational signatures continue to be generated, and if so their temporal patterns of activity, subsets of cell lines were cultured in vitro for extended periods and subjected to single cell cloning and whole genome or exome sequencing or directly to single cell whole genome sequencing. As expected, signatures of past exogenous exposures, such as tobacco smoke and ultraviolet light, were not generated in vitro. In contrast, signatures of normal and defective DNA repair and replication continued to be generated at essentially constant mutation rates. Signatures of APOBEC cytidine deaminase DNA-editing activity exhibited a distinctive pattern with substantial fluctuations in mutation rate over time and episodic bursts of mutations. The initiating factors for these bursts are unclear although retrotransposon mobilisation may play a role. This cell line set now constitutes a comprehensive resource of live experimental models of mutational processes of both known and unknown aetiologies potentially retaining the patterns of activity and regulatory influences operative in human cells in vivo.

Data Use Conditions


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Label Code Version Modifier
obsolete general research use and clinical care DUO:0000005 2017-10-16
obsolete research use only DUO:0000014 2017-10-16
publication required DUO:0000019 2017-10-16
user specific restriction DUO:0000026 2017-10-16
institution specific restriction DUO:0000028 2017-10-16