Mutation signatures including APOBEC in cancer cell lines

32Citations
Citations of this article
83Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Background: Multiple endogenous and exogenous sources of DNA damage contribute to the overall mutation burden in cancer, with distinct and overlapping combinations contributing to each cancer type. Many mutation sources result in characteristic mutation signatures, which can be deduced from tumor genomic DNA sequences. Examples include spontaneous hydrolytic deamination of methyl-cytosine bases in CG motifs (AGEING signature) and C-to-T and C-to-G mutations in 5'-TC(A/T) motifs (APOBEC signature). Methods: The deconstructSigs R package was used to analyze single-base substitution mutation signatures in more than 1000 cancer cell lines. Two additional approaches were used to analyze the APOBEC mutation signature. Results: Most cell lines show evidence for multiple mutation signatures. For instance, the AGEING signature, which is the largest source of mutation in most primary tumors, predominates in the majority of cancer cell lines. The APOBEC mutation signature is enriched in cancer cell lines from breast, lung, head/neck, bladder, and cervical cancers, where this signature also comprises a large fraction of all mutations. Conclusions: The single-base substitution mutation signatures of cancer cell lines often reflect those of the original tumors from which they are derived. Cancer cell lines with enrichments for distinct mutation signatures such as APOBEC have the potential to become model systems for fundamental research on the underlying mechanisms and for advancing clinical strategies to exploit these processes.

Cite

CITATION STYLE

APA

Jarvis, M. C., Ebrahimi, D., Temiz, N. A., & Harris, R. S. (2018). Mutation signatures including APOBEC in cancer cell lines. JNCI Cancer Spectrum, 2(1). https://doi.org/10.1093/jncics/pky002

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free