Table 1.
Relapse-associated genes in diffuse large B-cell lymphoma (DLBCL).
| Study | Cohort Description | Cohort Size | Method | Genes Presenting R/R Enriched Variants in Paired Diagnosis-Relapse Analyses 1 | Genes Presenting R/R Enriched Variants in Comparison with Independent Primary Cohorts 2 |
|---|---|---|---|---|---|
| Jiang et al. 2014 [46] | Paired D-R samples |
N = 7 (4/7 tLY) |
WES | BCL2, EP300, B2M, CD58 | |
| Morin et al. 2016 [51] | Paired D-R/R samples |
N = 12 (9/12 tLY) |
Targeted panel | STAT6, EZH2, FOXO1, SOCS1, KMT2D, CD79B, NFKBIE | |
| R/R samples (taken after at least one cycle of immuno-chemotherapy) |
N = 25 | WES Targeted panel |
R/R samples compared with independent primary cohort: KMT2C, MPEG1, NFKBIZ, CCND3, STAT6, TP53, MYC, FOXO1 |
||
| Juskevicius et al. 2016 [45] | Paired D-R samples (relapse following complete remission) |
N = 20 | Targeted panel |
KMT2D, MEF2B, TET2, PRDM1,
PTEN, EBF1 |
|
| Non-relapsing samples (taken at diagnosis ≥4 years relapse-free) |
N = 20 | Targeted panel | Diagnosis samples of relapsed patients compared with non-relapsing samples: KMT2D, BCL2, PTEN, PRDM1, MCL1, CARD11 |
||
| Melchardt et al. 2016 [44] | Paired D-R/R samples | N = 24 | Targeted panel |
TP53, RB1, EZH2 | Diagnosis samples of R/R patients compared with independent primary cohort: NOTCH1, SMARCA4, PIM1, KMT2D R/R samples compared with independent primary cohort: TP53, BCL2, MYC, RB1, ATM, EZH2 |
| Park et al. 2016 [55] | Diagnosis samples of responsive (CR maintained > 1 year interval) vs. refractory patients (<1 year interval) |
N = 7 responsive N = 6 refractory |
WES | TP53, MYD88, B2M, PRDM15, FNBP4, AHR, CEP128, BRE, SORCS3, WDFY3, CXXC4 | |
| Mareschal et al. 2016 [54] | Diagnosis samples of R/R patients (≤1 year interval) |
N = 14 | WES | ABC: MYD88, TBL1XR1, IRF4, CD58, PCDH17, HIST1H1B, HIST1H1C, HIST1H1D GCB: BCL2, DUSP2, NFKBIA, BTG2, MEF2B |
|
| Greenawalt et al. 2017 [52] | Paired D-R/R samples | N = 8 | WES | CREBBP, BCL2 | |
| R/R samples (after 1–8 cycles of R-CHOP) |
N = 47 | R/R samples compared with independent primary cohort: CREBBP, BCL2, TP53, B2M, MYC, BTK |
|||
| Nijland et al. 2018 [53] | Paired D-R/R samples (patients that received 6–8 cycles of R-CHOP) |
N = 6 | WES | SOCS1, PIM1, MYC, BCL2, BIRC3, BTG2, IRF4, SGK1, B2M, CALR, HLA-DR, HLA-B | Diagnosis and relapsed samples of R/R cohort compared with independent primary cohort: SOCS1, PIM1, MYC, HLA-DR, HLA-B |
| Rushton et al. 2020 [34] | Paired D-R/R samples (tissue biopsies/ctDNA) |
N = 57 | Targeted panel | MS4A1, KMT2D, CD79B, TBL1XR1, ZFP36L1, CARD11, BTG2, MYC, SOCS1, PIM1, TNFAIP3, MYD88, HIST1H1E, NFKBIE, TNFRSF14, BCL2, IRF4, SGK1, GNA13, B2M, FBXO11, TP53, CD58, EP300 | |
| R/R ctDNA | N = 135 | R/R samples compared with independent primary cohort: KMT2D, TP53, CREBBP, FOXO1, NFKBIE, MS4A1 |
|||
| Isaev et al. 2020 [48] | Paired D-CNS relapse samples |
N = 5 | WES | PIM1, ETV6 | |
| Diagnosis samples of systemic and CNS relapsed patients (<1 year interval) vs. non-relapsing patients (≥5 years relapse free) |
N = 62 systemic relapse N = 72 CNS relapse N = 89 Non-relapsing |
Targeted panel WES |
Diagnosis samples of CNS relapse compared with non-relapsing samples: MYD88, CD79B, PIM1 Diagnosis samples of refractory disease or systemic relapse compared with non-relapsing samples: TP53, MYD88, BCL2, HIST1H1E, HIST1H1C, FOXO1, BTG1, CIITA, CD58, ZFP36L1 |
TLY, Transformed lymphoma; D-R, diagnosis-relapse; R/R, relapse/refractory; CNS, central nervous system; ctDNA, circulating tumor DNA; WES, whole exome sequencing; 1 Genes were selected in case of gain of variant allele frequency (VAF) and/or presence of relapse-specific mutations in the R/R samples in matched DLBCL diagnosis-relapse analyses; 2 Genes were selected in case of higher mutational frequency in diagnosis and/or relapsed samples of R/R cohort compared with primary DLBCL cohort(s).