Mutational signatures: the patterns of somatic mutations hidden in cancer genomes

Abstract

All cancers originate from a single cell that starts to behave abnormally due to the acquired somatic mutations in its genome. Until recently, the knowledge of the mutational processes that cause these somatic mutations has been very limited. Recent advances in sequencing technologies and the development of novel mathematical approaches have allowed deciphering the patterns of somatic mutations caused by different mutational processes. Here, we summarize our current understanding of mutational patterns and mutational signatures in light of both the somatic cell paradigm of cancer research and the recent developments in the field of cancer genomics.

Figure 1

Mutational processes operative in a cancer. This simulated example illustrates four distinct mutational processes with variable strengths operative at different times throughout the lifetime of the patient. Each of these processes has a unique mutational signature exemplified by the six classes of somatic substitutions. At the beginning, all mutations in the cell (from which the cancer was eventually developed) were due to the activity of the endogenous mutational process 1. As time progresses, the other mutational process get activated and the spectrum of the cell continues to change. Note that the final sequenced cancer genome does not resemble any of the operative mutational signatures.