Table 2.
Significantly enriched individual somatic mutations, as well as genes significantly affected by non-synonymous somatic mutations, observed in more than two MUTYH positive tumors.
| Gene | Variant (context) | MUTYH positives | MUTYH negatives | p-value | SBS18/36 relative likelihood (MUTYH positives vs MUTYH negatives) |
|---|---|---|---|---|---|
| KRAS | c.34G>T p.G12C (CCA>A) | 16/19 (84%) | 127/5364 (2.4%) | 2 × 10−23 | 62% |
| PIK3CA | c.1636C>A p.Q546K (GCA>A) | 7/19 (37%) | 36/5364 (0.7%) | 6 × 10−11 | 83% |
| KRAS | Gene-wide | 17/19 (89%) | 2025/5364 (38%) | 5 × 10−6 | 58% vs 17% |
| AMER1 | Gene-wide | 9/19 (47%) | 592/5364 (11%) | 8 × 10−5 | 35% vs 12% |
| PIK3CA | Gene-wide | 10/19 (53%) | 934/5364 (17%) | 5 × 10−4 | 60% vs 12% |
| ROBO2 | Gene-wide | 3/19 (16%) | 55/5364 (1.0%) | 1 × 10−3 | 42% vs 20% |
| TAF1L | Gene-wide | 5/19 (26%) | 420/5364 (8%) | 0.01 | 36% vs 13% |
| SMAD4 | Gene-wide | 6/19 (32%) | 638/5364 (12%) | 0.02 | 36% vs 13% |
| SMAD2 | Gene-wide | 4/19 (21%) | 308/5364 (6%) | 0.02 | 53% vs 13% |
| APC | Gene-wide | 17/19 (89%) | 3468/5364 (65%) | 0.03 | 45% vs 18% |
| ERBB3 | Gene-wide | 4/19 (21%) | 388/5352 (7%) | 0.045 | 47% vs 13% |
Somatic mutations observed in the significantly enriched genes in MUTYH positives were more often associated with the trinucleotide contexts related to the SBS18/36 tumor mutational signatures (TMS) as measured by the SBS18/36 relative likelihood. P-values were calculated with Fisher’s exact test (two-sided).