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Sequencing shows that large B-cell lymphoma is at least seven diseases, each defined by which faults occur together. The classification explains a great deal about how the disease behaves and currently changes almost nothing about how it is treated.
Two groups sequenced large series in 2018 and arrived at overlapping answers. Exome and transcriptome sequencing with copy-number analysis across 574 biopsies produced four prominent subtypes named for the lesions that co-occur: MCD for MYD88 L265P with CD79B mutation, BN2 for BCL6 fusions with NOTCH2 mutations, N1 for NOTCH1 mutations, and EZB for EZH2 mutations with BCL2 translocations; survival after immunochemotherapy was better in BN2 and EZB and worse in MCD and N1 (Schmitz 2018). Consensus clustering of 304 primary tumours found five subsets, including a low-risk activated B-cell group of extrafollicular or marginal-zone origin, two germinal-centre subsets with different outcomes, and a group defined by biallelic TP53 inactivation and CDKN2A loss that cuts across cell of origin entirely (Chapuy 2018).
LymphGen is what made these usable on one patient: an algorithm that returns the probability that a lymphoma belongs to one of seven genetic subtypes, and which showed that each subtype shares a pathogenesis with a particular indolent or extranodal lymphoma, so the groups are not statistical artefacts (Wright 2020).
The limits matter. It needs a sequencing panel that calls mutations, copy number and fusions, not a stain. A substantial share of cases come back unclassified. No regulator licenses anything on a LymphGen call, and no randomised trial has assigned treatment by it. Its real effect so far has been on how trials are designed and how their subgroups are read: the concentration of BTK inhibitor activity in the MCD and N1 subtypes is the clearest example, and it is why the current first-line trials genotype everyone.
In plain words · MYD88 (Myeloid differentiation primary response protein MyD88) is a gene that drives cell growth when it is altered. The public catalogues list it as a drug target, an oncogene driver and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Non-Hodgkin lymphoma, Leukaemia, Breast cancer and 4 more.
Showing the target this term concerns: MYD88.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
Shares EZH2 gain-of-function mutation (Tyr646, originally Tyr641), Cell of origin (GCB vs ABC), BCL6, The germinal centre reaction.
Shares B-cell receptor / BTK signalling (to NF-κB), Inflammation & NF-κB, Marginal zone lymphoma, Non-Hodgkin lymphoma (all types).
Shares B-cell receptor / BTK signalling (to NF-κB), Inflammation & NF-κB, Marginal zone lymphoma, Non-Hodgkin lymphoma (all types).
Shares EZH2 gain-of-function mutation (Tyr646, originally Tyr641), The germinal centre reaction, BCL-2, Non-Hodgkin lymphoma (all types).
Shares B-cell receptor / BTK signalling (to NF-κB), Waldenström macroglobulinaemia, Marginal zone lymphoma, Next-generation sequencing (NGS).
Shares Primary CNS lymphoma, Waldenström macroglobulinaemia, Marginal zone lymphoma, Next-generation sequencing (NGS).
Shares BCL6, The germinal centre reaction, BCL-2, Non-Hodgkin lymphoma (all types).
Shares CDKN2A, Waldenström macroglobulinaemia, Marginal zone lymphoma, TP53.