Frequency of recurrent driver events in RS
| . | Percent in discovery cohort (n = 52) . | Percent in total cohort (n = 97) . | Pathway impacted (focal events only) . |
|---|---|---|---|
| del(17p) | 63.5 | 52.6 | DNA damage |
| TP53 | 55.8 | 43.3 | DNA damage |
| NOTCH1 | 40.4 | 39.2 | NOTCH signaling |
| del(13q14.2) | 25.0 | 29.9 | |
| del(9p21.3)[CDKN2A/B] | 19.2 | 27.8 | Cell cycle/DNA damage |
| del(9p) | 26.9 | 24.7 | |
| SF3B1 | 19.2 | 21.6 | RNA splicing |
| del(1p) | 23.1 | 20.6 | |
| IRF2BP2 | 13.5 | 19.6 | B-cell transcription-inflammation |
| Tri(12) | 15.4 | 19.6 | |
| del(6q) | 19.2 | 18.6 | |
| del(9q) | 23.1 | 18.6 | |
| del(15q15.1)[MGA] | 21.2 | 17.5 | B-cell transcription-MYC activation |
| amp(1q23.1) | 23.1 | 16.5 | Antiapoptotic signaling |
| del(11q22.3)[ATM] | 15.4 | 15.5 | Cell cycle/DNA damage |
| del(7q36.2)[EZH2, KMT2C] | 11.5 | 15.5 | Chromatin remodeling |
| WGD | 17.3 | 15.5 | |
| amp(7p) | 15.4 | 15.5 | |
| del(14q32.11) | 19.2 | 13.4 | |
| amp(8q24.21)[MYC] | 15.4 | 13.4 | B-cell transcription-MYC activation |
| del(2q37.1) | 15.4 | 12.4 | |
| del(8q12.1) | 11.5 | 12.4 | |
| XPO1 | 9.6 | 12.4 | Nuclear export |
| EGR2 | 11.5 | 11.3 | B-cell transcription |
| MGA | 11.5 | 11.3 | B-cell transcription-MYC activation |
| PIM1 | 9.6 | 11.3 | |
| SPEN | 11.5 | 10.3 | NOTCH signaling/B-cell transcription |
| del(16q12.1) | 11.5 | 9.3 | |
| del(3p21.32)[SETD2] | 7.7 | 9.3 | Chromatin remodeling |
| amp(13q31.2) | 11.5 | 9.3 | |
| KRAS | 11.5 | 9.3 | BCR signaling |
| MYC | 5.8 | 9.3 | B-cell transcription-MYC activation |
| amp(11q23.1)[POU2AF1] | 7.7 | 9.3 | B-cell transcription |
| del(10q) | 5.8 | 9.3 | Inflammatory signaling |
| ATM | 5.8 | 8.2 | Cell cycle/DNA damage |
| BRAF | 5.8 | 8.2 | BCR signaling |
| del(12p13.2) | 5.8 | 8.2 | |
| del(19p13.3) | 7.7 | 8.2 | |
| del(1p35.3)[ARID1A] | 5.8 | 8.2 | Chromatin remodeling |
| del(1q42.13) | 7.7 | 8.2 | |
| amp(16q23.2)[IRF8] | 7.7 | 8.2 | B-cell transcription-inflammation |
| del(18q22.2) | 7.7 | 7.2 | |
| DNMT3A | 7.7 | 7.2 | DNA methylation |
| amp(7q21.2)[CDK6] | 11.5 | 7.2 | Cell cycle/DNA damage |
| amp(9p24.1)[PD-L1/PD-L2] | 7.7 | 7.2 | Immune evasion |
| IRF8 | 7.7 | 7.2 | B-cell transcription-inflammation |
| CARD11 | 7.7 | 6.2 | BCR signaling |
| del(8p21.3) | 7.7 | 5.2 | |
| HIST1H1E | 7.7 | 5.2 | Chromatin-histone |
| SRSF1 | 5.8 | 5.2 | RNA splicing |
| MYD88 | 1.9 | 5.2 | Inflammatory signaling |
| PRDM1 | 3.8 | 5.2 | B-cell transcription |
| del(13q14.2) [RB1] | 7.7 | 5.2 | DNA damage |
| TET2 | 5.8 | 5.1 | DNA methylation |
| B2M | 5.8 | 4.1 | Immune evasion |
| CCND3 | 1.9 | 4.1 | Cell cycle/DNA damage |
| CHD2 | 5.8 | 4.1 | Chromatin remodeling |
| amp(19p13.2) | 7.7 | 4.1 | |
| amp(6p22.1)[IRF4] | 5.8 | 4.1 | B-cell transcription-inflammation |
| GNB1 | 5.8 | 4.1 | BCR signaling |
| TBL1XR1 | 5.8 | 4.1 | RNA processing |
| ZC3H18 | 5.8 | 4.1 | RNA processing |
| amp(18q21.33) | 1.9 | 3.1 | |
| HIST1H2AC | 3.8 | 3.1 | Chromatin-histone |
| EZH2 | 5.8 | 3.1 | Chromatin remodeling |
| NFKBIE | 5.8 | 3.1 | Inflammatory signaling |
| . | Percent in discovery cohort (n = 52) . | Percent in total cohort (n = 97) . | Pathway impacted (focal events only) . |
|---|---|---|---|
| del(17p) | 63.5 | 52.6 | DNA damage |
| TP53 | 55.8 | 43.3 | DNA damage |
| NOTCH1 | 40.4 | 39.2 | NOTCH signaling |
| del(13q14.2) | 25.0 | 29.9 | |
| del(9p21.3)[CDKN2A/B] | 19.2 | 27.8 | Cell cycle/DNA damage |
| del(9p) | 26.9 | 24.7 | |
| SF3B1 | 19.2 | 21.6 | RNA splicing |
| del(1p) | 23.1 | 20.6 | |
| IRF2BP2 | 13.5 | 19.6 | B-cell transcription-inflammation |
| Tri(12) | 15.4 | 19.6 | |
| del(6q) | 19.2 | 18.6 | |
| del(9q) | 23.1 | 18.6 | |
| del(15q15.1)[MGA] | 21.2 | 17.5 | B-cell transcription-MYC activation |
| amp(1q23.1) | 23.1 | 16.5 | Antiapoptotic signaling |
| del(11q22.3)[ATM] | 15.4 | 15.5 | Cell cycle/DNA damage |
| del(7q36.2)[EZH2, KMT2C] | 11.5 | 15.5 | Chromatin remodeling |
| WGD | 17.3 | 15.5 | |
| amp(7p) | 15.4 | 15.5 | |
| del(14q32.11) | 19.2 | 13.4 | |
| amp(8q24.21)[MYC] | 15.4 | 13.4 | B-cell transcription-MYC activation |
| del(2q37.1) | 15.4 | 12.4 | |
| del(8q12.1) | 11.5 | 12.4 | |
| XPO1 | 9.6 | 12.4 | Nuclear export |
| EGR2 | 11.5 | 11.3 | B-cell transcription |
| MGA | 11.5 | 11.3 | B-cell transcription-MYC activation |
| PIM1 | 9.6 | 11.3 | |
| SPEN | 11.5 | 10.3 | NOTCH signaling/B-cell transcription |
| del(16q12.1) | 11.5 | 9.3 | |
| del(3p21.32)[SETD2] | 7.7 | 9.3 | Chromatin remodeling |
| amp(13q31.2) | 11.5 | 9.3 | |
| KRAS | 11.5 | 9.3 | BCR signaling |
| MYC | 5.8 | 9.3 | B-cell transcription-MYC activation |
| amp(11q23.1)[POU2AF1] | 7.7 | 9.3 | B-cell transcription |
| del(10q) | 5.8 | 9.3 | Inflammatory signaling |
| ATM | 5.8 | 8.2 | Cell cycle/DNA damage |
| BRAF | 5.8 | 8.2 | BCR signaling |
| del(12p13.2) | 5.8 | 8.2 | |
| del(19p13.3) | 7.7 | 8.2 | |
| del(1p35.3)[ARID1A] | 5.8 | 8.2 | Chromatin remodeling |
| del(1q42.13) | 7.7 | 8.2 | |
| amp(16q23.2)[IRF8] | 7.7 | 8.2 | B-cell transcription-inflammation |
| del(18q22.2) | 7.7 | 7.2 | |
| DNMT3A | 7.7 | 7.2 | DNA methylation |
| amp(7q21.2)[CDK6] | 11.5 | 7.2 | Cell cycle/DNA damage |
| amp(9p24.1)[PD-L1/PD-L2] | 7.7 | 7.2 | Immune evasion |
| IRF8 | 7.7 | 7.2 | B-cell transcription-inflammation |
| CARD11 | 7.7 | 6.2 | BCR signaling |
| del(8p21.3) | 7.7 | 5.2 | |
| HIST1H1E | 7.7 | 5.2 | Chromatin-histone |
| SRSF1 | 5.8 | 5.2 | RNA splicing |
| MYD88 | 1.9 | 5.2 | Inflammatory signaling |
| PRDM1 | 3.8 | 5.2 | B-cell transcription |
| del(13q14.2) [RB1] | 7.7 | 5.2 | DNA damage |
| TET2 | 5.8 | 5.1 | DNA methylation |
| B2M | 5.8 | 4.1 | Immune evasion |
| CCND3 | 1.9 | 4.1 | Cell cycle/DNA damage |
| CHD2 | 5.8 | 4.1 | Chromatin remodeling |
| amp(19p13.2) | 7.7 | 4.1 | |
| amp(6p22.1)[IRF4] | 5.8 | 4.1 | B-cell transcription-inflammation |
| GNB1 | 5.8 | 4.1 | BCR signaling |
| TBL1XR1 | 5.8 | 4.1 | RNA processing |
| ZC3H18 | 5.8 | 4.1 | RNA processing |
| amp(18q21.33) | 1.9 | 3.1 | |
| HIST1H2AC | 3.8 | 3.1 | Chromatin-histone |
| EZH2 | 5.8 | 3.1 | Chromatin remodeling |
| NFKBIE | 5.8 | 3.1 | Inflammatory signaling |
Data from Parry et al, Evolutionary history of transformation from chronic lymphocytic leukemia to Richter syndrome. Nat Med. 2023;29(1):158-169,15 with permission from Springer Nature.