Table 1.
Overview of cSNVs and confirmed somatic mutations in most frequently mutated genes
| Cases | Total | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Gene | NS | S | T | NS | S | T | Somatic cSNVs (RNA-seq cohort)* | P (raw) | q | NS SP | T SP | Skew (M, WT, both) *** |
| MLL2† | 16 | 8 | 17 | 17 | 8 | 18 | 10 | 6.85×10-8 | 8.50×10-7 | 0.834 | 14.4 | WT |
| TNFRSF14 G† | 7 | 1 | 7 | 8 | 1 | 7 | 11 | 6.85×10-8 | 8.50×10-7 | 7.52 | 118 | both |
| SGK1 G† | 18 | 6 | 6 | 37 | 10 | 6 | 9 | 6.85×10-8 | 8.50×10-7 | 19.5 | 61.7 | - |
| BCL10† | 2 | 0 | 4 | 3 | 0 | 4 | 4 | 6.85×10-8 | 8.50×10-7 | 3.62 | 112 | WT |
| GNA13 G† | 21 | 1 | 2 | 33 | 1 | 2 | 5 | 6.85×10-8 | 8.50×10-7 | 24.1 | 25.7 | both |
| TP53 G† | 20 | 2 | 1 | 23 | 3 | 1 | 22 | 6.85×10-8 | 8.50×10-7 | 15.6 | 14.1 | both |
| EZH2 G† | 33 | 0 | 0 | 33 | 0 | 0 | 33 | 6.85×10-8 | 8.50×10-7 | 11.4 | 0.00 | both |
| BTG2† | 12 | 6 | 1 | 14 | 6 | 1 | 2 | 6.85×10-8 | 8.50×10-7 | 23.9 | 35.1 | - |
| BCL2 G† | 42 | 45 | 0 | 96 | 105 | 0 | 43 | 9.35×10-8 | 8.50×10-7 | 3.78 | 0.00 | M |
| BCL6†** | 11 | 2 | 0 | 12 | 2 | 0 | 2 | 9.35×10-8 | 8.50×10-7 | 0.175 | 0.00 | M |
| CIITA†** | 5 | 3 | 0 | 6 | 3 | 0 | 2 | 9.35×10-8 | 8.50×10-7 | 0.086 | 0.00 | |
| FAS† | 2 | 0 | 4 | 3 | 0 | 4 | 2 | 1.52×10-7 | 1.17×10-6 | 2.54 | 66.5 | WT |
| BTG1† | 11 | 6 | 2 | 11 | 7 | 2 | 10 | 1.52×10-7 | 1.17×10-6 | 17.5 | 52.5 | both |
| MEF2B G† | 20 | 2 | 0 | 20 | 2 | 0 | 10 | 2.05×10-7 | 1.47×10-6 | 14.2 | 0.00 | M |
| IRF8† | 11 | 5 | 3 | 14 | 5 | 3 | 3 | 4.55×10-7 | 3.03×10-6 | 8.82 | 28.2 | WT |
| TMEM30A† | 1 | 0 | 4 | 1 | 0 | 4 | 4 | 6.06×10-7 | 3.79×10-6 | 0.785 | 65.0 | WT |
| CD58† | 2 | 0 | 3 | 2 | 0 | 3 | 2 | 2.42×10-6 | 1.43×10-5 | 2.29 | 69.2 | - |
| KLHL6† | 10 | 2 | 2 | 12 | 2 | 2 | 4 | 1.00×10-5 | 5.26×10-5 | 5.42 | 16.4 | - |
| MYD88 A† | 13 | 2 | 0 | 14 | 2 | 0 | 9 | 1.00×10-5 | 5.26×10-5 | 12.4 | 0.00 | WT |
| CD70† | 5 | 0 | 1 | 5 | 0 | 2 | 3 | 1.70×10-5 | 8.48×10-5 | 7.08 | 44.0 | - |
| CD79B A† | 7 | 2 | 1 | 9 | 2 | 1 | 5 | 2.00×10-5 | 9.52×10-5 | 10.9 | 18.3 | M |
| CCND3† | 7 | 1 | 2 | 7 | 1 | 2 | 6 | 2.80×10-5 | 1.27×10-4 | 6.55 | 36.3 | WT |
| CREBBP† | 20 | 7 | 4 | 24 | 7 | 4 | 9 | 1.00×10-4 | 4.35×10-4 | 2.72 | 6.04 | both |
| HIST1H1C† | 9 | 0 | 0 | 10 | 0 | 0 | 6 | 1.80×10-4 | 7.50×10-4 | 11.9 | 0.00 | both |
| B2M† | 7 | 0 | 0 | 7 | 0 | 0 | 4 | 3.90×10-4 | 1.56×10-3 | 16.6 | 0.00 | WT |
| ETS1† | 10 | 1 | 0 | 10 | 1 | 0 | 4 | 4.10×10-4 | 1.58×10-3 | 5.76 | 0.00 | WT |
| CARD11† | 14 | 3 | 0 | 14 | 3 | 0 | 3 | 1.90×10-3 | 7.04×10-3 | 3.37 | 0.00 | both |
| FAT2†** | 2 | 1 | 0 | 2 | 1 | 0 | 2 | 6.30×10-3 | 2.25×10-2 | 0.128 | 0.00 | - |
| IRF4†** | 9 | 4 | 0 | 26 | 5 | 0 | 5 | 7.00×10-3 | 2.41×10-2 | 0.569 | 0.00 | both |
| FOXO1† | 8 | 4 | 0 | 10 | 4 | 0 | 4 | 7.60×103 | 2.53×10-2 | 4.02 | 0.00 | - |
| STAT3 | 9 | 0 | 0 | 9 | 0 | 0 | 4 | 2.19×10-2 | 6.08×10-2 | - | - | both |
| RAPGEF1 | 8 | 3 | 0 | 10 | 3 | 0 | 3 | 2.98×10-2 | 7.45×10-2 | - | - | WT |
| ABCA7 | 12 | 3 | 0 | 15 | 3 | 0 | 2 | 7.76×10-2 | 1.67×10-1 | - | - | WT |
| RNF213 | 10 | 8 | 0 | 10 | 8 | 0 | 2 | 7.87×10-2 | 1.67×10-1 | - | - | - |
| MUC16 | 17 | 12 | 0 | 39 | 25 | 0 | 2 | 8.32×10-2 | 1.73×10-1 | - | - | - |
| HDAC7 | 8 | 4 | 0 | 8 | 4 | 0 | 2 | 8.94×10-2 | 1.82×10-1 | - | - | WT |
| PRKDC | 7 | 3 | 0 | 7 | 4 | 0 | 2 | 1.06×10-1 | 2.05×10-1 | - | - | - |
| SAMD9 | 9 | 2 | 0 | 9 | 2 | 0 | 2 | 1.79×10-1 | 3.01×10-1 | - | - | - |
| TAF1 | 10 | 0 | 0 | 10 | 0 | 0 | 2 | 3.03×10-1 | 4.74×10-1 | - | - | - |
| PIM1 | 20 | 19 | 0 | 33 | 34 | 0 | 11 | 3.40×10-1 | 5.23×10-1 | - | - | WT |
| COL4A2 | 8 | 2 | 0 | 8 | 2 | 0 | 2 | 7.64×10-1 | 8.99×10-1 | - | - | - |
| EP300 | 8 | 7 | 1 | 8 | 7 | 1 | 3 | 9.54×10-1 | 1.00 | - | - | WT |
Individual cases with nonsynonymous (NS), synonymous (S) and truncating (T) mutations and total number of mutations of each class is shown separately as some genes contained multiple mutations in the same case. The P values indicated in bold are the upper limit on the P value for that gene determined with the approach described by Greenman et al (see Methods)19, q is the Benjamini-corrected q value, and NS, SP and T SP refer to selective pressure estimates from this model for the acquisition of nonsynonymous or truncating mutations, respectively.
genes significant at an FDR of 0.03. SNVs in BCL2 and previously confirmed hot spot mutations in EZH2 and CD79B are likely somatic in these samples based on published observations of others.
Additional somatic mutations identified in larger cohorts and insertion/deletion mutations are not included in this total.
Selective pressure estimates are both <1 indicating purifying selection rather than positive selection acting on this gene.
“both” indicates we observed separate cases in which skewed expression was seen but where this skew was not consistent for the mutant or wild-type allele. Genes with a superscript of either A or G were found to have mutations significantly enriched in ABC or GCB cases, respectively (P< 0.05, Fisher Exact test).