Application of the LymphGen classification tool to 928 clinically and genetically‐characterised cases of diffuse large B cell lymphoma (DLBCL)

Runge, Hendrik F. P.; Lacy, Stuart; Barrans, Sharon; Beer, Philip; Painter, Daniel; Smith, Alexandra; Roman, Eve; Combes, Burton; Crouch, Simon; Tooze, Reuben; Hodson, Daniel J.

doi:10.1111/bjh.17132

Cited by 37 publications

(50 citation statements)

References 9 publications

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“…A further modification of the HMRN classification used the presence of MYC hotspot and NOTCH1 PEST domain mutations to identify a NOTCH1 and BCL2-MYC subgroups. 41 This modified HMRN classifier showed high concordance when cases were reclassified using the NCI LymphGen classifier (Fig 4).…”

Section: Genomic Profiling Of Dlbclmentioning

confidence: 88%

“…A recent publication applied the LymphGen classifier to cases classified in the HMRN study and showed high concordance with the original HMRN assignment. 41 Indeed, the greatest source of variability was the number of cases classified at all rather than the movement between subtypes (Fig 5B). LymphGen assigned a unique classification to 53% of cases, whereas HMRN classified 73% of cases.…”

Section: Challenges Of Implementing Molecular Subtypingmentioning

confidence: 96%

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Molecular profiling in diffuse large B‐cell lymphoma: why so many types of subtypes?

2021

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The term diffuse large B-cell lymphoma (DLBCL) includes a heterogeneous collection of biologically distinct tumours. This heterogeneity currently presents a barrier to the successful deployment of novel, biologically targeted therapies. Molecular profiling studies have recently proposed new molecular classification systems. These have the potential to resolve the biological heterogeneity of DLBCL into manageable subgroups of tumours that rely on shared oncogenic programmes. In many cases these biological programmes straddle the boundaries of our existing systems for classifying B-cell lymphomas. Here we review the findings from these major molecular profiling studies with a specific focus on those that propose new genetic subgroups of DLBCL. We highlight the areas of consensus and discordance between these studies and discuss the implications for current clinical practice and for clinical trials. Finally, we address the outstanding challenges and solutions to the introduction of genomic subtyping and precision medicine in DLBCL.

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Section: Genomic Profiling Of Dlbclmentioning

confidence: 88%

Section: Challenges Of Implementing Molecular Subtypingmentioning

confidence: 96%

Molecular profiling in diffuse large B‐cell lymphoma: why so many types of subtypes?

2021

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“…The classification of DLBCL has recently been transformed by the discovery of genetic subtypes based on patterns of co-occurring genetic alterations (Chapuy et al, 2018;Lacy et al, 2020;Schmitz et al, 2018;Wright et al, 2020). At least seven genetic subtypes are recognized currently and have been reproducibly identified in four large DLBCL cohorts (Runge et al, 2021;Wright et al, 2020). Importantly, the DLBCL genetic subtypes differ with respect to pathogenesis, phenotypic properties, oncogenic survival pathways, and responses to therapy (Chapuy et al, 2018;Lacy et al, 2020;Schmitz et al, 2018;Wright et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL

Wilson¹,

Wright²,

Huang³

et al. 2021

Cancer Cell

205

145

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“…Several classification methods compared to LymphGen classification have been reported using the UK-HMRN cohort data. 12 Modified HMRN classification 27 with the LymphGen classification (69%). The two-step classifier 28 is a simple algorithm and also had good sensitivity and specificity; however, the concordance rate with the Lymph-Gen classification was not satisfactory in all cases (54%).…”

Section: Discussionmentioning

confidence: 99%

Genetic subtype classification using a simplified algorithm and mutational characteristics of diffuse large B‐cell lymphoma in a Japanese cohort

et al. 2021

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Summary Recent large‐scale genetic studies have proposed a new genetic classification of diffuse large B‐cell lymphoma (DLBCL), which is clinically and biologically heterogeneous. However, the classification methods were complicated to be introduced into clinical practice. Here we retrospectively evaluated the mutational status and copy number changes of 144 genes in 177 Japanese patients with DLBCL, using targeted DNA sequencing. We developed a simplified algorithm for classifying four genetic subtypes—MYD88, NOTCH2, BCL2, and SGK1—by assessing alterations in 18 representative genes and BCL2 and BCL6 rearrangement status, integrating the significant genes from previous studies. In our cohort and another validation cohort from published data, the classification results in our algorithm showed close agreement with the other established algorithm. A differential prognosis among the four groups was observed. The NOTCH2 group showed a particularly poorer outcome than similar groups in previous reports. Furthermore, our study revealed unreported genetic features in the DLBCL subtypes that are mainly reported in Japanese patients, such as CD5‐positive DLBCL and methotrexate‐associated lymphoproliferative disorders. These results indicate the utility of our simplified method for DLBCL genetic subtype classification, which can facilitate the optimisation of treatment strategies. In addition, our study highlights the genetic features of Japanese patients with DLBCL.

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Application of the LymphGen classification tool to 928 clinically and genetically‐characterised cases of diffuse large B cell lymphoma (DLBCL)

Abstract: A Phase II study of a nonmyeloablative allogeneic stem cell transplant with peritransplant rituximab in patients with BCell lymphoid malignancies: favorably durable event-free survival in chemosensitive patients.

Cited by 37 publications

References 9 publications

Molecular profiling in diffuse large B‐cell lymphoma: why so many types of subtypes?

Molecular profiling in diffuse large B‐cell lymphoma: why so many types of subtypes?

Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL

Genetic subtype classification using a simplified algorithm and mutational characteristics of diffuse large B‐cell lymphoma in a Japanese cohort

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