Mutation of chromatin modifiers; an emerging hallmark of germinal center B-cell lymphomas

Matthew A Lunning, M. R. Green

Research output: Contribution to journalReview article

33 Citations (Scopus)

Abstract

Subtypes of non-Hodgkin's lymphomas align with different stages of B-cell development. Germinal center B-cell (GCB)-like diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Burkitt's lymphoma (BL) each share molecular similarities with normal GCB cells. Recent next-generation sequencing studies have gained insight into the genetic etiology of these malignancies and revealed a high frequency of mutations within genes encoding proteins that modifying chromatin. These include activating and inactivating mutations of genes that perform post-translational modification of histones and organize chromatin structure. Here, we discuss the function of histone acetyltransferases (CREBBP, EP300), histone methyltransferases (KDM2C/D, EZH2) and regulators of higher order chromatin structure (HIST1H1C/D/E, ARID1A and SMARCA4) that have been reported to be mutated in ≥5% of DLBCL, FL or BL. Mutations of these genes are an emerging hallmark of lymphomas with GCB-cell origins, and likely represent the next generation of therapeutic targets for these malignancies.

Original languageEnglish (US)
Article numbere361
JournalBlood Cancer Journal
Volume5
Issue number10
DOIs
StatePublished - Oct 16 2015

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Germinal Center
B-Cell Lymphoma
Chromatin
B-Lymphocytes
Mutation
Follicular Lymphoma
Burkitt Lymphoma
Lymphoma, Large B-Cell, Diffuse
Histone Acetyltransferases
Mutation Rate
Post Translational Protein Processing
Histones
Non-Hodgkin's Lymphoma
Genes
Lymphoma
Neoplasms
Proteins
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Mutation of chromatin modifiers; an emerging hallmark of germinal center B-cell lymphomas. / Lunning, Matthew A; Green, M. R.

In: Blood Cancer Journal, Vol. 5, No. 10, e361, 16.10.2015.

Research output: Contribution to journalReview article

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abstract = "Subtypes of non-Hodgkin's lymphomas align with different stages of B-cell development. Germinal center B-cell (GCB)-like diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Burkitt's lymphoma (BL) each share molecular similarities with normal GCB cells. Recent next-generation sequencing studies have gained insight into the genetic etiology of these malignancies and revealed a high frequency of mutations within genes encoding proteins that modifying chromatin. These include activating and inactivating mutations of genes that perform post-translational modification of histones and organize chromatin structure. Here, we discuss the function of histone acetyltransferases (CREBBP, EP300), histone methyltransferases (KDM2C/D, EZH2) and regulators of higher order chromatin structure (HIST1H1C/D/E, ARID1A and SMARCA4) that have been reported to be mutated in ≥5{\%} of DLBCL, FL or BL. Mutations of these genes are an emerging hallmark of lymphomas with GCB-cell origins, and likely represent the next generation of therapeutic targets for these malignancies.",
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