Comparison of main clusters
| Current study . | Chapuy et al17 . | Schmitz et al16 . | Notes . |
|---|---|---|---|
| MYD88 | C5 | MCD | Strongly associated with ABC-type DLBCL. The most robust group, occurring in all reports. Contains the majority of cases with PCNSL and primary testicular lymphoma. Associated with a poor prognosis |
| MYD88, PIM1, CD79B, ETV6, CDKN2A | CD79B, MYD88, ETV6, PIM1, TBL1XR1 | MYD88, CD79B | |
| BCL2 | C3 | EZB | Strongly associated with GCB-type DLBCL. Mutational profile is shared with follicular lymphoma. Contains the majority of cases of transformed follicular lymphoma and cases with a concurrent diagnosis of follicular lymphoma. Generally favorable prognosis, although enriched for cases of double-hit lymphoma and MHG |
| EZH2, BCL2, CREBBP, TNFRSF14, KMT2D | BCL2, CREBBP2, EZH2, KMT2D, TNFRSF14 | BCL2 translocation, EZH2 | |
| SOCS1/SGK1 | C4 | Predominantly GCB-type DLBCL. Shares genetic and gene expression features of PMBCL. Associated with the most favorable prognosis | |
| SOCS1, CD83, SGK1, NFKBIA, HIST1H1E | SGK1, HIST1H1E, NFKBIE, BRAF, CD83 | ||
| TET2/SGK1 | A less strongly identifiable subtype emerging from SGK1 when applying the Akaike information criterion (supplemental Methods). Has very strong similarity to SOCS1/SGK1 but differentiated by the addition of TET2 and BRAF and the lack of SOCS1 and CD83. Associated with a favorable prognosis | ||
| TET2, BRAF, SGK1, KLHL6, ID3 | |||
| NOTCH2 | C1 | BN2 | Not associated with any cell of origin. Shares mutational similarity to MZL but not enriched for cases of transformed MZL. Less strongly defined than other subgroups (supplemental Methods) |
| NOTCH2, BCL10, TNFAIP3, CCND3, SPEN | BCL6 translocation, BCL10, TNFAIP3, UBE2A, CD70 | BCL6 translocation, NOTCH2 | |
| NEC | Other | A default category, containing cases that could not be classified elsewhere. Contains cases with no detected mutation. Likely to also contain cases belonging to both NOTCH1 and TP53/CNA subgroups. Even though 3 abnormalities are significantly enriched in this group, their q-values are far less extreme than those of characteristic mutations from the other subtypes | |
| NOTCH1, REL amplification, TP53 | |||
| C2 | Characterized by TP53 mutation and widespread copy number changes. Due to limited CNA in our study, these cases were predominantly allocated to the NEC group | ||
| TP53, frequent deletions | |||
| C0 | Cases with no detectable mutation were allocated to the NEC group | ||
| No detected abnormalities | |||
| N1 | Characterized by NOTCH1 mutation, this was significantly elevated in our NEC group but only mutated in 2.5% of samples. Associated with poor outcome | ||
| NOTCH1 |
| Current study . | Chapuy et al17 . | Schmitz et al16 . | Notes . |
|---|---|---|---|
| MYD88 | C5 | MCD | Strongly associated with ABC-type DLBCL. The most robust group, occurring in all reports. Contains the majority of cases with PCNSL and primary testicular lymphoma. Associated with a poor prognosis |
| MYD88, PIM1, CD79B, ETV6, CDKN2A | CD79B, MYD88, ETV6, PIM1, TBL1XR1 | MYD88, CD79B | |
| BCL2 | C3 | EZB | Strongly associated with GCB-type DLBCL. Mutational profile is shared with follicular lymphoma. Contains the majority of cases of transformed follicular lymphoma and cases with a concurrent diagnosis of follicular lymphoma. Generally favorable prognosis, although enriched for cases of double-hit lymphoma and MHG |
| EZH2, BCL2, CREBBP, TNFRSF14, KMT2D | BCL2, CREBBP2, EZH2, KMT2D, TNFRSF14 | BCL2 translocation, EZH2 | |
| SOCS1/SGK1 | C4 | Predominantly GCB-type DLBCL. Shares genetic and gene expression features of PMBCL. Associated with the most favorable prognosis | |
| SOCS1, CD83, SGK1, NFKBIA, HIST1H1E | SGK1, HIST1H1E, NFKBIE, BRAF, CD83 | ||
| TET2/SGK1 | A less strongly identifiable subtype emerging from SGK1 when applying the Akaike information criterion (supplemental Methods). Has very strong similarity to SOCS1/SGK1 but differentiated by the addition of TET2 and BRAF and the lack of SOCS1 and CD83. Associated with a favorable prognosis | ||
| TET2, BRAF, SGK1, KLHL6, ID3 | |||
| NOTCH2 | C1 | BN2 | Not associated with any cell of origin. Shares mutational similarity to MZL but not enriched for cases of transformed MZL. Less strongly defined than other subgroups (supplemental Methods) |
| NOTCH2, BCL10, TNFAIP3, CCND3, SPEN | BCL6 translocation, BCL10, TNFAIP3, UBE2A, CD70 | BCL6 translocation, NOTCH2 | |
| NEC | Other | A default category, containing cases that could not be classified elsewhere. Contains cases with no detected mutation. Likely to also contain cases belonging to both NOTCH1 and TP53/CNA subgroups. Even though 3 abnormalities are significantly enriched in this group, their q-values are far less extreme than those of characteristic mutations from the other subtypes | |
| NOTCH1, REL amplification, TP53 | |||
| C2 | Characterized by TP53 mutation and widespread copy number changes. Due to limited CNA in our study, these cases were predominantly allocated to the NEC group | ||
| TP53, frequent deletions | |||
| C0 | Cases with no detectable mutation were allocated to the NEC group | ||
| No detected abnormalities | |||
| N1 | Characterized by NOTCH1 mutation, this was significantly elevated in our NEC group but only mutated in 2.5% of samples. Associated with poor outcome | ||
| NOTCH1 |
MZL, marginal zone lymphoma.