# A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications

Source: https://onco.cc/key-papers/paper-wright-lymphgen-genetic-subtypes-dlbcl-cancer-cell-2020/  
OnCo record `paper-wright-lymphgen-genetic-subtypes-dlbcl-cancer-cell-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A tool that takes one patient's tumour genetics and gives the probability that it belongs to each of seven genetic groups, rather than sorting whole cohorts into clusters.

## Summary

Clustering methods classify a cohort. A patient needs a classification of their own tumour, with a statement of how confident it is. LymphGen is the algorithm that provides it: it returns the probability that a given lymphoma belongs to each of seven genetic subtypes on the basis of its genetic features.

The classification extends the four subtypes of the 2018 National Cancer Institute paper and revealed genetic similarities between diffuse large B-cell lymphoma subtypes and various indolent and extranodal lymphoma types, which suggests a shared pathogenesis and is one of the stronger arguments that the current histological boundaries do not cut the disease at its joints. The subtypes have distinct gene-expression profiles, distinct immune microenvironments and distinct outcomes after immunochemotherapy, and functional analysis of subtype models showed distinct vulnerabilities to targeted therapy.

LymphGen is now the classifier used to select patients in genetics-directed trials in this disease, which is the practical reason it belongs on this list rather than in a methods appendix.

## Fields

- Kind: Key paper
- Last checked: 2026-10-01
- Also known as: LymphGen; Wright 2020; Seven genetic subtypes of diffuse large B-cell lymphoma
- Tags: lymphoma-evidence
- Journal: Cancer Cell
- Year: 2020
- DOI: 10.1016/j.ccell.2020.03.015
- Authors: Wright GW, Huang DW, Phelan JD, et al.
- Findings: An algorithm was described that returns the probability that an individual patient's lymphoma belongs to each of seven genetic subtypes, based on its genetic features.; The classification revealed genetic similarities between these subtypes and various indolent and extranodal lymphoma types, suggesting shared pathogenesis.; The genetic subtypes have distinct gene-expression profiles, distinct immune microenvironments and distinct outcomes after immunochemotherapy.; Functional analysis of genetic subtype models highlighted distinct vulnerabilities to targeted therapy.
- What it means: The piece that turns a research classification into something a trial can use on one person's biopsy, with a probability attached rather than a flat label. It is the reason genetics-directed lymphoma trials became possible at all.
- Caveats: A classification tool, not a clinical trial: no randomised evidence yet shows that treating by LymphGen subtype improves outcomes.; It needs comprehensive genetic data, including copy number and structural variants, which most routine panels do not generate.; A proportion of cases remain unclassified by design, and that proportion is larger in cohorts with less complete sequencing.; Subtype boundaries still depend on the training cohorts, which were largely of European ancestry.

## Sources

- Cancer Cell 2020: https://doi.org/10.1016/j.ccell.2020.03.015
- PubMed: https://pubmed.ncbi.nlm.nih.gov/32289277/
- Europe PMC: https://europepmc.org/article/MED/32289277

## Connected records

- key papers: [Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray](https://onco.cc/key-papers/paper-hans-immunohistochemistry-cell-of-origin-dlbcl-blood-2004/), [Genetics and pathogenesis of diffuse large B-cell lymphoma](https://onco.cc/key-papers/paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018/), [Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes](https://onco.cc/key-papers/paper-chapuy-molecular-subtypes-dlbcl-nat-med-2018/)
- roadmaps: [Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting](https://onco.cc/roadmaps/lymphoma-roadmap/)
- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Marginal zone lymphoma](https://onco.cc/cancers/marginal-zone-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Primary CNS lymphoma](https://onco.cc/cancers/primary-cns-lymphoma/), [Primary mediastinal (thymic) large B-cell lymphoma](https://onco.cc/cancers/primary-mediastinal-b-cell-lymphoma/)
- fronts: [AI & Computation](https://onco.cc/fronts/ai-computation/), [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- technologies: [Whole-exome & whole-genome sequencing](https://onco.cc/technologies/wes-wgs/)
- terms: [Cell of origin (GCB vs ABC)](https://onco.cc/terms/cell-of-origin/), [Next-generation sequencing (NGS)](https://onco.cc/terms/ngs/)
- targets: [BCL-2](https://onco.cc/targets/bcl2/), [BCL6](https://onco.cc/targets/bcl6/), [CD79b](https://onco.cc/targets/cd79b/), [EZH2](https://onco.cc/targets/ezh2/), [MYD88](https://onco.cc/targets/myd88/), [NOTCH1](https://onco.cc/targets/notch1/), [NOTCH2](https://onco.cc/targets/notch2/), [TP53](https://onco.cc/targets/tp53/)
- institutions: [National Cancer Institute (NIH)](https://onco.cc/institutions/nci/)
- people: [Louis M. Staudt](https://onco.cc/people/louis-staudt/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Data silos](https://onco.cc/bottlenecks/b-data-silos/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- journals: [Cancer Cell](https://onco.cc/journals/cancer-cell/)
- ideas: [Assign first-line treatment in diffuse large B-cell lymphoma by genetic subtype, not by a three-antibody stain](https://onco.cc/ideas/lymphoma-ev-genetic-subtype-directed-first-line/)

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