Exploration_of__mutational_processes_in_human_cancer_cell_lines__Exome

Approximately 25 cell lines representative of 11 mutation signatures have been selected and will be grown from a single cell, referred to as parental clone, for a period of 3 months to allow accumulation of mutations. Following that period, we will obtain 2 subclones from each of the parental clone for sequencing analysis. In total we will be sequencing 2 parental clones and 4 subclones per cell line for approximately 25 cell lines.

Type: Cancer Genomics
Archiver: European Genome-Phenome Archive (EGA)

2 Datasets 3 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001004201	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.	Illumina HiSeq 2000 Illumina HiSeq 2500	75
EGAD00001004203	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.	HiSeq X Ten	192

Publications	Citations
Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis. Petljak M, Alexandrov LB, Brammeld JS, Price S, Wedge DC, Grossmann S, Dawson KJ, Ju YS, Iorio F, Tubio JMC, Koh CC, Georgakopoulos-Soares I, Rodríguez-Martín B, Otlu B, O'Meara S, Butler AP, Menzies A, Bhosle SG, Raine K, Jones DR, Teague JW, Beal K, Latimer C, O'Neill L, Zamora J, Anderson E, Patel N, Maddison M, Ng BL, Graham J, Garnett MJ, McDermott U, Nik-Zainal S, Campbell PJ, Stratton MR. Cell 176: 2019 1282-1294.e20	367
Mapping clustered mutations in cancer reveals APOBEC3 mutagenesis of ecDNA. Bergstrom EN, Luebeck J, Petljak M, Khandekar A, Barnes M, Zhang T, Steele CD, Pillay N, Landi MT, Bafna V, Mischel PS, Harris RS, Alexandrov LB. Nature 602: 2022 510-517	127
Uncovering the role of LINE-1 in the evolution of lung adenocarcinoma. Zhang T, Zhao W, Wirth C, Díaz-Gay M, Yin J, Cecati M, Marchegiani F, Hoang PH, Leduc C, Baine MK, Travis WD, Sholl LM, Joubert P, Sang J, McElderry JP, Antony M, Klein A, Khandekar A, Hartman C, Rosenbaum J, Colón-Matos FJ, Miraftab M, Saha M, Lee OW, Jones KM, Caporaso NE, Wong MP, Leung KC, Hsiung CA, Chen CY, Edell ES, Santamaría JM, Schabath MB, Yendamuri SS, Manczuk M, Lissowska J, Świątkowska B, Mukeria A, Shangina O, Zaridze D, Holcatova I, Mates D, Milosavljevic S, Savic M, Bossé Y, Rothberg BEG, Christiani DC, Gaborieau V, Brennan P, Liu G, Hofman P, Homer R, Yang SR, Pesatori AC, Consonni D, Yang L, Zhu B, Shi J, Brown K, Rothman N, Chanock SJ, Alexandrov LB, Choi J, Cardelli M, Lan Q, Nowak MA, Wedge DC, Landi MT. Nature None: 2025 None	3