Mutational Signatures (v3 - May 2019)

Introduction

Somatic mutations are present in all cells of the human body and occur throughout life. They are the consequence of multiple mutational processes, including the intrinsic slight infidelity of the DNA replication machinery, exogenous or endogenous mutagen exposures, enzymatic modification of DNA and defective DNA repair. Different mutational processes generate unique combinations of mutation types, termed “Mutational Signatures”.

In the past few years, large-scale analyses have revealed many mutational signatures across the spectrum of human cancer types. However, as the number of mutational signatures grows the need for a curated census of signatures has become apparent. Here, we deliver such a resource by providing the profiles of, and additional information about, known mutational signatures.

Vignettes

As the number of mutational signatures has increased it has become increasingly difficult to keep in mind their mutational features, aetiology, and other attributes. We therefore provide a summary “vignette” for each mutational signature. The vignettes include mutational profiles and notes on potential aetiology, associated mutational signatures, how the signature has changed during iterations of analysis and other pertinent comments. These are intended to be short, very high level, “aides-memoire” for key elements of what we know, suspect or has been widely discussed for each signature. They are not intended to be comprehensive summaries of everything reported in the scientific literature and they are not referenced.

These pages present vignettes for three sets of signatures:

The signatures were extracted by SigProfiler as described in Alexandrov, L.B. et al., 2020. With a few exceptions, the signatures were extracted from the 2,780 whole-genome variant calls produced by the ICGC/TCGA Pan Cancer Analysis of Whole Genomes (PCAWG) Network. The signatures are available in numerical form from synapse.org ID syn12009743, and attributions of the signatures to mutations in tumors are available from synapse.org IDs syn11804040 and syn11804058. The stability and reproducibility of the signatures were assessed on somatic mutations from an additional 1,865 whole genomes and 19,148 exomes.

All input data and references for original sources are available from synapse.org ID syn11801889.

Versions

Mutational signatures version 3 were released as part of COSMIC release v89 (May 2019). The version 3 update expands and improves upon the version 2 signatures (March 2015) that were part of earlier COSMIC releases. You can still view the previous mutational signatures: