Table 2. Summary of the MM-PSN subgroups.
DE, differentially expressed. The symbols ↑ and ↓ indicate positive and negative enrichment in column 3 (Selected enriching features) and up- and down-regulated genes in column 5 (Selected DE genes), respectively. AKTi, AKT inhibitor.
| Group/Subgroup | Size (n) |
Selected enriching
features |
Median
PFS; OS (days) |
Selected DE
genes |
Selected enriched
pathways |
Selected drug
candidates |
Selected
essential genes |
| 1: HD | 357 | HD; mutations in NRAS; AC092691.1:LSAMP, CEP164P1:RPS19, and TPM4:SIK1 fusions |
1094; N/A | - | Inflammation and immune evasion |
- | - |
| 1a: HD/-7− | 100 | HD with no gain of chromosome 7; TPM4:SIK1 fusion; mutational signatures: SBS1 (clock-like) ↑; low clonal complexity |
1082; N/A |
TNF↑, H19↑, KIT↑, FRZB↑, ASS1↓, ETV4↓ |
Interferon signaling, CD40 signaling, IL12 and IL18 signaling, JAK2 targets, DNA repair, cell cycle |
Carboplatin + paclitaxel + sorafenib, palbociclib, NOTCH1 antibody, vandetanib + everolimus, dinaciclib + AKTi |
APOC1, EBF1, MYT1L, PAX5 |
| 1b: HD/tMYC | 105 | HD with MYC translocation; mutations in NRAS; mutational signatures: SBS1 (clock-like)↑; SBS2 and SBS13 (APOBEC)↓ |
1297; N/A |
FAS↓, PIK3R3↑, TIMP1↓, AHR↓, CCR5↑, IL4R↓ |
Unfolded protein response, DNA repair, MET signaling, PI3K-AKT activation by MET, MYC targets, ATR signaling, TRAIL signaling |
Onartuzumab, crizotinib, palbociclib, cetuximab, pictilisib, alpelisib, taselisib, NOTCH1 antibody, Nutlin-3, vandetabib + everolimus, sorafenib |
CCDC78, HOXC4, TMEM121, MYC |
| 1c: HD/tMYC/1q+ | 103 | HD with MYC translocation and 1q gain age > 65 years old; higher number of female patients |
677; N/A |
GRM3↑, GDA↑, FLT3↓, CKB↑ |
IL27 signaling, MYC targets, MET signaling, MAPK1 activation, IRF4 targets |
NOTCH1 antibody, onartuzumab, crizotinib, dinaciclib + AKTI, vandetanib + everolimus |
CCND2, CALCB, CST6, MYT1L |
| 1d: MultiDel | 49 | Multiple chromosome deletions including 1p, 17, 4p, 4q, 8q, 16p, 16q, 13q, and 14q |
1240; 1777 |
EREG↑, LAMC3↑, CXCR5↓, EPCAM↑, MYCN↑, CCND2↑ |
Down-regulation of interferon response, integrin signaling, IL1, IL2 and IL15 signaling, MTOR, FOXO, WNT signaling |
Irinotecan, pictilisib |
CCND2, KRT7 |
| 2: tMMSET/tMAF | 166 | Translocations of MMSET and MAF; gain of 1q; deletion of 13q and 14q; mutations in FGFR3, PRKD2, and DIS3 |
751*; N/A | - | Proliferative signaling | - | - |
| 2a: tMMSET | 38 | Translocation of MMSET; deletion of 12p, 13q, 14q, and 22q; mutations in PRKD2; mutational signatures: SBS5 (clock-like)↑; SBS9 (polymerase ƞ and somatic hypermutation)↑ |
917 (N/A) | MMSET↑, AR↑, TIMP1↑, FLT4↑ |
Cancer testis antigens, FGFR3 signaling |
Tazemetostat, selumetinib, abemaciclib |
CCND2, OVOL2, PFKP, FGFR3 |
| 2b: tMAF | 36 | Translocation of MAF/ MAFA/MAFB; mutations in FLG; ITGB7 fusions; gain of 1q; deletion of 13q, 16q, and 22q; higher number of female patients; high GSS; mutational signatures: SBS2 and SBS13 (APOBEC)↑; SBS5 (clock-like)↓; SBS6 (MMR)↓; SBS10b (POLE-Exo)↑ |
903; 1500 | MAF↑, MAFA↑, NTRKK2↑, CDK6↑, CDKN2B↑, IL4R↑, AR↓, IL6↓, DKK1↓ |
Hypoxia, IL3 and IL4 signaling, Hedgehog, IGF1, PTEN, VEGF, IL2-STAT5 and HES signaling, activation of NTRK2, O-linked mucin glycosylation |
Trametinib, abemaciclib, tenovin-6, anti-TACI |
CCND2, MAF, CDK6, EEF2KMT, NFIA, RHPN1 |
| 2c: 1q | 28 | Gain of 1q; deletion of 13q, 14q, and 16q; mutations in TRAF3; mutational signatures: SBS1 (clock-like)↓ |
610; N/A |
CD4↑, ERBB3↑, IL32↑, ITGB1↑ |
ERK signaling, down-regulation of CTLA4 inhibitory signal, B cell survival |
Trametinib, abemaciclib |
CCND2, AQP7, GIA3, ZNF676 |
| 2d: tMMSET/1q+/15q+ | 24 | Translocation of MMSET; mutations in FGFR3; gain of 1q, 3p, 3q, and 15q; deletion of 13q |
1031; N/A |
ALB↑, MAGEC2↑, CXCL12↓, IL18↓, CCND2↑, MAF↑ |
B-Arrestins, FGFR3 signaling |
Infigratinib, erdafitinib |
CCND2, MAF, IRS2, FGFR3, BAMBI |
| 2e: tMMSET/1q+ | 40 | Translocation of MMSET; mutations in FGFR3 and DIS3; gain of 1q (highest number of copies); deletion of 13q; mutational signatures: SBS1 (clock-like)↓; SBS2 (APOBEC)↑; SBS10b (POLE-Exo) ↑; high clonal complexity |
624; 1033 |
IGF1R↑, MME↑, PAX9↑, MIAT↑, FGFR3↑, CCND2↑ |
FAS, FGFR3, KRAS, and IL2-STAT5 signaling |
Olaparib, trametinib, abermaciclib, erdafitinib, IKKB inhibitor, anti–NY-ESO-1 |
CCND2, MAF, FGFR3, BAMBI, IGF1R |
| 3: tCCND1 | 132 | Translocation of CCND1; gain of 11q; CCND1;KLF2. FOSB:KLF6 and C21orf91:CHODL fusions |
1130; NA | - | Replicative immortality and evasion of growth suppression |
- | - |
| 3a: tCCND1 | 36 | Translocation of CCND1; low GSS; low clonal complexity |
1176; N/A | CCND1↑, MMP9↑, ERG↑, KDR↑, IL18↑, IRF8↑ |
Inflammasomes, complement cascade, apoptosis, Waldenström macroglobulinemia, amyloid fiber formation, MDM2 targets |
Omipalisib, RAFi HG6-64-1, abemaciclib, trametinib |
CCND1, MT2A, MT1G, APOC1 |
| 3b: tCCND1/11q+/13q+ | 73 | Translocation of CCND1; gain of 11q and 13q; focal gain of 13q12.11; biallegic inactivation of TP53; CCND1:KLF2 fusion; low GSS; mutational signatures: SBS1 (clock-like)↓; SBS2 (APOBEC)↓; SBS6(MMR)↑ |
1236; N/A |
CCND1↑, SLC7A11↑, SALL4↑, TP73↑ |
Apoptosis, MDM2 targets, IL2-STAT5 signaling |
Venetoclax, trametinib, RAFi HG6-64-1, abermaciclib |
RUNX1T1, DMKN, BATF3 |
| 3c: tCCND1/1q+ | 23 | Translocation of CCND1 gain of 1q; deletion of 16q |
832; 1590 | CCND1↑, MS4A1↑, KREMEN2↑ |
MDS high-risk signature, APOBEC, MDM2 targets |
RAFi HG6-64-1, abermaciclib, trametinib |
CCND1, ZNF676 |