BCL-6 mRNA expression in higher grade transformation of follicle center lymphoma

Correlation with somatic mutations in the 5′ regulatory region of the BCL-6 gene

Izidore Lossos, R. Warnke, R. Levy

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Follicle center lymphoma (FCL) is an indolent low-grade B cell non-Hodgkin's lymphoma (NHL) that frequently transforms to aggressive diffuse large B cell lymphoma (DLBCL). Histological transformation of FCL is commonly associated with accumulation of secondary genetic alterations. The BCL-6 gene is commonly implicated in the pathogenesis of DLBCL and its expression may be altered by clonal rearrangements and somatic point mutations in its 5′ non-translated regulatory region. Recently, somatic mutations of the BCL-6 gene were associated with the transformation process. Here, we examined BCL-6 mRNA expression and BCL-6 mutations in paired biopsies from the same patients obtained at the time of FCL diagnosis and after transformation. BCL-6 mRNA expression markedly increased upon transformation (1.9- to 4.8-fold) in three cases, remained unchanged in one case and decreased compared to the diagnosis FCL specimens in four cases. The three specimens that demonstrated an increase in the BCL-6 mRNA expression upon transformation harbored BCL-6 gene mutations in the 5′ region of the first intron that overlapped with the previously reported negative regulatory region of the gene. Accumulation of new mutations in this region was not observed in DLBCL biopsies in which the BCL-6 mRNA expression did not increase. The present study demonstrates that although BCL-6 gene mutations do accumulate during the transformation process and, depending on their location within the first intron, may deregulate BCL-6 mRNA expression, increase in BCL-6 mRNA expression is not uniformly required for transformation from FCL to DLBCL.

Original languageEnglish
Pages (from-to)1857-1862
Number of pages6
JournalLeukemia
Volume16
Issue number9
DOIs
StatePublished - Sep 1 2002
Externally publishedYes

Fingerprint

Nucleic Acid Regulatory Sequences
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Messenger RNA
Mutation
Genes
B-Cell Lymphoma
Introns
Biopsy
Regulator Genes
Point Mutation
Non-Hodgkin's Lymphoma

Keywords

  • Follicle center lymphoma
  • Mutations
  • Transformation

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

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title = "BCL-6 mRNA expression in higher grade transformation of follicle center lymphoma: Correlation with somatic mutations in the 5′ regulatory region of the BCL-6 gene",
abstract = "Follicle center lymphoma (FCL) is an indolent low-grade B cell non-Hodgkin's lymphoma (NHL) that frequently transforms to aggressive diffuse large B cell lymphoma (DLBCL). Histological transformation of FCL is commonly associated with accumulation of secondary genetic alterations. The BCL-6 gene is commonly implicated in the pathogenesis of DLBCL and its expression may be altered by clonal rearrangements and somatic point mutations in its 5′ non-translated regulatory region. Recently, somatic mutations of the BCL-6 gene were associated with the transformation process. Here, we examined BCL-6 mRNA expression and BCL-6 mutations in paired biopsies from the same patients obtained at the time of FCL diagnosis and after transformation. BCL-6 mRNA expression markedly increased upon transformation (1.9- to 4.8-fold) in three cases, remained unchanged in one case and decreased compared to the diagnosis FCL specimens in four cases. The three specimens that demonstrated an increase in the BCL-6 mRNA expression upon transformation harbored BCL-6 gene mutations in the 5′ region of the first intron that overlapped with the previously reported negative regulatory region of the gene. Accumulation of new mutations in this region was not observed in DLBCL biopsies in which the BCL-6 mRNA expression did not increase. The present study demonstrates that although BCL-6 gene mutations do accumulate during the transformation process and, depending on their location within the first intron, may deregulate BCL-6 mRNA expression, increase in BCL-6 mRNA expression is not uniformly required for transformation from FCL to DLBCL.",
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AU - Levy, R.

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N2 - Follicle center lymphoma (FCL) is an indolent low-grade B cell non-Hodgkin's lymphoma (NHL) that frequently transforms to aggressive diffuse large B cell lymphoma (DLBCL). Histological transformation of FCL is commonly associated with accumulation of secondary genetic alterations. The BCL-6 gene is commonly implicated in the pathogenesis of DLBCL and its expression may be altered by clonal rearrangements and somatic point mutations in its 5′ non-translated regulatory region. Recently, somatic mutations of the BCL-6 gene were associated with the transformation process. Here, we examined BCL-6 mRNA expression and BCL-6 mutations in paired biopsies from the same patients obtained at the time of FCL diagnosis and after transformation. BCL-6 mRNA expression markedly increased upon transformation (1.9- to 4.8-fold) in three cases, remained unchanged in one case and decreased compared to the diagnosis FCL specimens in four cases. The three specimens that demonstrated an increase in the BCL-6 mRNA expression upon transformation harbored BCL-6 gene mutations in the 5′ region of the first intron that overlapped with the previously reported negative regulatory region of the gene. Accumulation of new mutations in this region was not observed in DLBCL biopsies in which the BCL-6 mRNA expression did not increase. The present study demonstrates that although BCL-6 gene mutations do accumulate during the transformation process and, depending on their location within the first intron, may deregulate BCL-6 mRNA expression, increase in BCL-6 mRNA expression is not uniformly required for transformation from FCL to DLBCL.

AB - Follicle center lymphoma (FCL) is an indolent low-grade B cell non-Hodgkin's lymphoma (NHL) that frequently transforms to aggressive diffuse large B cell lymphoma (DLBCL). Histological transformation of FCL is commonly associated with accumulation of secondary genetic alterations. The BCL-6 gene is commonly implicated in the pathogenesis of DLBCL and its expression may be altered by clonal rearrangements and somatic point mutations in its 5′ non-translated regulatory region. Recently, somatic mutations of the BCL-6 gene were associated with the transformation process. Here, we examined BCL-6 mRNA expression and BCL-6 mutations in paired biopsies from the same patients obtained at the time of FCL diagnosis and after transformation. BCL-6 mRNA expression markedly increased upon transformation (1.9- to 4.8-fold) in three cases, remained unchanged in one case and decreased compared to the diagnosis FCL specimens in four cases. The three specimens that demonstrated an increase in the BCL-6 mRNA expression upon transformation harbored BCL-6 gene mutations in the 5′ region of the first intron that overlapped with the previously reported negative regulatory region of the gene. Accumulation of new mutations in this region was not observed in DLBCL biopsies in which the BCL-6 mRNA expression did not increase. The present study demonstrates that although BCL-6 gene mutations do accumulate during the transformation process and, depending on their location within the first intron, may deregulate BCL-6 mRNA expression, increase in BCL-6 mRNA expression is not uniformly required for transformation from FCL to DLBCL.

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