Table 2. Significant associations between mutational signatures and driver mutations within individual cancer types, alongside proposed aetiology and frequency of the trinucleotide context in the associated mutational signature.
| Mutational signature | Proposed aetiology of mutational signature* | Driver mutation | Protein change | Odds ratio (OR) | Cancer type# | Mutated samples in cancer type (%) | Trinucleotide context | Frequency of trinucleotide context in signature^ | |
|---|---|---|---|---|---|---|---|---|---|
| Amount (%) | Rank | ||||||||
| Signature 1 | Spontaneous deamination of 5-methylcytosine | IDH1 c.395G>A | p.R132H | Less than 1 | GBM | 4.97 | A[C>T]G | 17.16 | High |
| IDH1 c.395G>A | p.R132H | Less than 1 | LGG | 57.43 | A[C>T]G | 17.16 | High | ||
| Signature 2 | Activity of the AID/APOBEC family of cytidine deaminases | PIK3CA c.1633G>A | p.E545K | Greater than 1 | LUSC | 3.29 | T[C>T]A | 41.99 | High |
| PIK3CA c.1633G>A | p.E545K | Greater than 1 | HNSC | 4.9 | T[C>T]A | 41.99 | High | ||
| PIK3CA c.1633G>A | p.E545K | Greater than 1 | CESC | 14.19 | T[C>T]A | 41.99 | High | ||
| PIK3CA c.1633G>A | p.E545K | Greater than 1 | BRCA | 6.34 | T[C>T]A | 41.99 | High | ||
| ERBB2 c.929C>T | p.S310F | Greater than 1 | BLCA | 4.77 | T[C>T]C | 8.2 | High | ||
| PIK3CA c.1633G>A | p.E545K | Greater than 1 | BLCA | 7.29 | T[C>T]A | 41.99 | High | ||
| PIK3CA c.1624G>A | p.E542K | Greater than 1 | LUSC | 2.26 | T[C>T]A | 41.99 | High | ||
| PIK3CA c.1624G>A | p.E542K | Greater than 1 | BRCA | 3.85 | T[C>T]A | 41.99 | High | ||
| PIK3CA c.1624G>A | p.E542K | Greater than 1 | BLCA | 4.52 | T[C>T]A | 41.99 | High | ||
| Signature 6 | Defective DNA mismatch repair | PIK3CA c.3140A>G | p.H1047R | Greater than 1 | STAD | 3.83 | A[T>C]G | 2.17 | Low |
| KRAS c.38G>A | p.G13D | Greater than 1 | UCEC | 2.29 | G[C>T]C | 7.73 | High | ||
| KRAS c.38G>A | p.G13D | Greater than 1 | STAD | 2.87 | G[C>T]C | 7.73 | High | ||
| KRAS c.35G>A | p.G12D | Greater than 1 | UCEC | 6.29 | A[C>T]C | 1.63 | Low | ||
| BRAF c.1799T>A | p.V600E | Greater than 1 | CRC | 9.22 | G[T>A]G | 0.06 | Low | ||
| PTEN c.697C>T | p.R233* | Greater than 1 | UCEC | 4.95 | A[C>T]G | 9.08 | High | ||
| PIK3CA c.3140A>G | p.H1047R | Greater than 1 | CRC | 3.44 | A[T>C]G | 2.17 | Low | ||
| Signature 7 | Ultraviolet light exposure | BRAF c.1798G>A | p.V600M | Greater than 1 | SKCM | 8.44 | A[C>T]T | 0.43 | Low |
| Signature 10 | Altered activity of the error-prone polymerase POLE | POLE c.857C>G | p.P286R | Greater than 1 | UCEC | 4 | C[C>G]T | 0 | Low |
| PIK3CA c.263G>A | p.R88Q | Greater than 1 | UCEC | 5.9 | T[C>T]G | 21.41 | High | ||
| PIK3CA c.263G>A | p.R88Q | Greater than 1 | CRC | 2.53 | T[C>T]G | 21.41 | High | ||
| TP53 c.637C>T | p.R213* | Greater than 1 | CRC | 2.17 | T[C>T]G | 21.41 | High | ||
| PTEN c.389G>A | p.R130Q | Greater than 1 | UCEC | 4.76 | T[C>T]G | 21.41 | High | ||
| ARID1A c.5965C>T | p.R1989* | Greater than 1 | UCEC | 3.81 | T[C>T]G | 21.41 | High | ||
| Signature 13 |
Activity of the AID/APOBEC family of cytidine deaminases |
PPP2R1A c.536C>G | p.P179R | Greater than 1 | UCEC | 4.38 | C[C>G]C | 0.09 | Low |
| PIK3CA c.1633G>A | p.E545K | Greater than 1 | BLCA | 7.29 | T[C>T]A | 11.38 | High | ||
| PIK3CA c.1633G>A | p.E545K | Greater than 1 | HNSC | 4.9 | T[C>T]A | 11.38 | High | ||
| PIK3CA c.1633G>A | p.E545K | Greater than 1 | BRCA | 6.34 | T[C>T]A | 11.38 | High | ||
| PIK3CA c.1624G>A | p.E542K | Greater than 1 | UCEC | 3.24 | T[C>T]A | 11.38 | High | ||
| PIK3CA c.1624G>A | p.E542K | Greater than 1 | LUSC | 2.26 | T[C>T]A | 11.38 | High | ||
| ERBB2 c.929C>T | p.S310F | Greater than 1 | BLCA | 4.77 | T[C>T]C | 1.5 | Low | ||
| PIK3CA c.1633G>A | p.E545K | Greater than 1 | LUSC | 3.29 | T[C>T]A | 11.38 | High | ||
| Signature 14 | Loss of mismatch repair and polymerase proofreading | PTEN c.389G>A | p.R130Q | Greater than 1 | UCEC | 4.76 | T[C>T]G | 0.94 | Low |
| Signature 20 | Loss of mismatch repair and polymerase proofreading | KRAS c.35G>A | p.G12D | Greater than 1 | UCEC | 6.29 | A[C>T]C | 2.22 | Low |
| BCOR c.4376A>G | p.N1459S | Greater than 1 | UCEC | 5.14 | A[T>C]T | 0.73 | Low | ||
| Signature 26 | Defective DNA mismatch repair | PIK3CA c.3140A>G | p.H1047R | Greater than 1 | CRC | 3.44 | A[T>C]G | 5.18 | High |
| BRAF c.1799T>A | p.V600E | Greater than 1 | CRC | 9.22 | G[T>A]G | 0.14 | Low | ||
| TP53 c.817C>T | p.R273C | Greater than 1 | UCEC | 2.1 | G[C>T]G | 2.25 | Low | ||
* Proposed aetiology obtained from refs [5] and [9] and ‘Signatures of Mutational Processes in Human Cancer’ curated by the Catalogue of Somatic Mutations in Cancer (COSMIC) database [6, 7];
# List of abbreviations for each cancer type are given in Table 1;
^ Trinucleotide frequencies for mutational signatures are obtained from ‘Signatures of Mutational Processes in Human Cancer’ curated by the COSMIC database [6, 7]. Amount designates the percentage of all mutations in the signature that occur in the trinucleotide context of the specific driver mutation. The rank designates whether that mutation in its trinucleotide context is high (amount > 5%) or low (amount ≤ 5%) in the mutational signature.