Dissecting aggressive B-cell lymphoma through genomic analysis – What is clinically relevant?

David W. Scott, Lisa M Rimsza

Research output: Contribution to journalArticle

Abstract

The aggressive B-cell lymphomas are a diverse collection of cancers grouped together based on clinical behavior and derivation from B lymphocytes. Genomic analyses on these tumours are now translating into improved classification systems and identification of underpinning targetable biology. Simple karyotyping revealed key translocations involving MYC, BCL2, and BCL6 that have impacted lymphoma classification in the World Health Organization classification scheme. Subsequently, gene expression profiling identified molecular subgroups within the most common lymphoma, diffuse large B-cell lymphoma (DLBCL): activated B-cell-like and germinal centre B-cell-like. Finally, next generation sequencing has revealed a modest number of frequently mutated genes and a long list of infrequent mutations. The mutational landscapes involve diverse genes associated with dysregulated signalling, epigenetic modification, blockade of cellular differentiation, and immune evasion. These mutational “signatures” are enriched in the different aggressive lymphoma subtypes impacting phenotypes and identifying therapeutic targets. Challenges to implementing genomic assays into clinical practice remain.

Original languageEnglish (US)
JournalBest Practice and Research: Clinical Haematology
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

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B-Cell Lymphoma
B-Lymphocytes
Cells
Lymphoma
Immune Evasion
Karyotyping
Germinal Center
Lymphoma, Large B-Cell, Diffuse
Genes
Gene Expression Profiling
Epigenomics
Lymphocytes
Neoplasms
Gene expression
Phenotype
Tumors
Assays
Mutation
Health
Therapeutics

Keywords

  • Biomarkers
  • Gene expression
  • Genomics
  • Lymphoma
  • Precision medicine
  • Translocations

ASJC Scopus subject areas

  • Oncology
  • Clinical Biochemistry

Cite this

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title = "Dissecting aggressive B-cell lymphoma through genomic analysis – What is clinically relevant?",
abstract = "The aggressive B-cell lymphomas are a diverse collection of cancers grouped together based on clinical behavior and derivation from B lymphocytes. Genomic analyses on these tumours are now translating into improved classification systems and identification of underpinning targetable biology. Simple karyotyping revealed key translocations involving MYC, BCL2, and BCL6 that have impacted lymphoma classification in the World Health Organization classification scheme. Subsequently, gene expression profiling identified molecular subgroups within the most common lymphoma, diffuse large B-cell lymphoma (DLBCL): activated B-cell-like and germinal centre B-cell-like. Finally, next generation sequencing has revealed a modest number of frequently mutated genes and a long list of infrequent mutations. The mutational landscapes involve diverse genes associated with dysregulated signalling, epigenetic modification, blockade of cellular differentiation, and immune evasion. These mutational “signatures” are enriched in the different aggressive lymphoma subtypes impacting phenotypes and identifying therapeutic targets. Challenges to implementing genomic assays into clinical practice remain.",
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