Somatic mutations of the translocated bcl-2 gene are associated with morphologic transformation of follicular lymphoma to diffuse large-cell lymphoma

A. Matolcsy, R. A. Warnke, D. M. Knowles

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16 Citations (Scopus)

Abstract

Background: Ninety percent of low-grade follicular lymphomas (FLs) carry the t(14;18) translocation. This event juxtaposes the bcl-2 oncogene to the immunoglobulin (Ig) heavy-chain gene and leads to bcl-2 gene overexpression. Morphologic transformation of FL to high-grade lymphoma is associated with multiple secondary chromosomal abnormalities of the neoplastic cells. Design: To analyze whether additional structural alterations of the translocated bcl- 2 gene are associated with morphologic transformation of FL, we PCR- amplified, cloned, and sequenced the major breakpoint region (MBR) and the open reading frames (ORF) of the translocated bcl-2 oncogene in six paired samples of FL and subsequent diffuse large-cell lymphoma (DLL). Results: In five cases, FL and DLL cells were clonally related, as suggested by the identical MBR sequences, but in one case they were different. PCR single- strand conformation polymorphism (SSCP) and sequence analyses were performed for identification of structural alterations of the bcl-2 gene in the OFR region corresponding to the 239 amino acid p26-bcl-2a protein. In three of the six patients, a total of 11 point mutations of the ORF were detected in the DLL cells. Four of them, at positions 29, 46, 59, and 106, yielded amino acid replacements. Conclusions: These findings demonstrate that FL and DLL cells may be clonally related or unrelated. They also show that transformation of FL cells can be associated with somatic point mutations of the bcl-2 oncogene ORF sequence resulting in alteration of the p26-bcl-2a gene product.

Original languageEnglish
JournalAnnals of Oncology
Volume8
Issue numberSUPPL. 2
Publication statusPublished - 1997

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bcl-2 Genes
Follicular Lymphoma
Lymphoma, Large B-Cell, Diffuse
Mutation
Oncogenes
Open Reading Frames
Point Mutation
Non-Hodgkin's Lymphoma
Immunoglobulin Heavy Chain Genes
Amino Acids
Polymerase Chain Reaction
Chromosome Aberrations
Sequence Analysis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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title = "Somatic mutations of the translocated bcl-2 gene are associated with morphologic transformation of follicular lymphoma to diffuse large-cell lymphoma",
abstract = "Background: Ninety percent of low-grade follicular lymphomas (FLs) carry the t(14;18) translocation. This event juxtaposes the bcl-2 oncogene to the immunoglobulin (Ig) heavy-chain gene and leads to bcl-2 gene overexpression. Morphologic transformation of FL to high-grade lymphoma is associated with multiple secondary chromosomal abnormalities of the neoplastic cells. Design: To analyze whether additional structural alterations of the translocated bcl- 2 gene are associated with morphologic transformation of FL, we PCR- amplified, cloned, and sequenced the major breakpoint region (MBR) and the open reading frames (ORF) of the translocated bcl-2 oncogene in six paired samples of FL and subsequent diffuse large-cell lymphoma (DLL). Results: In five cases, FL and DLL cells were clonally related, as suggested by the identical MBR sequences, but in one case they were different. PCR single- strand conformation polymorphism (SSCP) and sequence analyses were performed for identification of structural alterations of the bcl-2 gene in the OFR region corresponding to the 239 amino acid p26-bcl-2a protein. In three of the six patients, a total of 11 point mutations of the ORF were detected in the DLL cells. Four of them, at positions 29, 46, 59, and 106, yielded amino acid replacements. Conclusions: These findings demonstrate that FL and DLL cells may be clonally related or unrelated. They also show that transformation of FL cells can be associated with somatic point mutations of the bcl-2 oncogene ORF sequence resulting in alteration of the p26-bcl-2a gene product.",
keywords = "bcl-2 oncogene, Diffuse large-cell lymphoma, Follicular lymphoma, Lymphoma transformation, Somatic mutation",
author = "A. Matolcsy and Warnke, {R. A.} and Knowles, {D. M.}",
year = "1997",
language = "English",
volume = "8",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "SUPPL. 2",

}

TY - JOUR

T1 - Somatic mutations of the translocated bcl-2 gene are associated with morphologic transformation of follicular lymphoma to diffuse large-cell lymphoma

AU - Matolcsy, A.

AU - Warnke, R. A.

AU - Knowles, D. M.

PY - 1997

Y1 - 1997

N2 - Background: Ninety percent of low-grade follicular lymphomas (FLs) carry the t(14;18) translocation. This event juxtaposes the bcl-2 oncogene to the immunoglobulin (Ig) heavy-chain gene and leads to bcl-2 gene overexpression. Morphologic transformation of FL to high-grade lymphoma is associated with multiple secondary chromosomal abnormalities of the neoplastic cells. Design: To analyze whether additional structural alterations of the translocated bcl- 2 gene are associated with morphologic transformation of FL, we PCR- amplified, cloned, and sequenced the major breakpoint region (MBR) and the open reading frames (ORF) of the translocated bcl-2 oncogene in six paired samples of FL and subsequent diffuse large-cell lymphoma (DLL). Results: In five cases, FL and DLL cells were clonally related, as suggested by the identical MBR sequences, but in one case they were different. PCR single- strand conformation polymorphism (SSCP) and sequence analyses were performed for identification of structural alterations of the bcl-2 gene in the OFR region corresponding to the 239 amino acid p26-bcl-2a protein. In three of the six patients, a total of 11 point mutations of the ORF were detected in the DLL cells. Four of them, at positions 29, 46, 59, and 106, yielded amino acid replacements. Conclusions: These findings demonstrate that FL and DLL cells may be clonally related or unrelated. They also show that transformation of FL cells can be associated with somatic point mutations of the bcl-2 oncogene ORF sequence resulting in alteration of the p26-bcl-2a gene product.

AB - Background: Ninety percent of low-grade follicular lymphomas (FLs) carry the t(14;18) translocation. This event juxtaposes the bcl-2 oncogene to the immunoglobulin (Ig) heavy-chain gene and leads to bcl-2 gene overexpression. Morphologic transformation of FL to high-grade lymphoma is associated with multiple secondary chromosomal abnormalities of the neoplastic cells. Design: To analyze whether additional structural alterations of the translocated bcl- 2 gene are associated with morphologic transformation of FL, we PCR- amplified, cloned, and sequenced the major breakpoint region (MBR) and the open reading frames (ORF) of the translocated bcl-2 oncogene in six paired samples of FL and subsequent diffuse large-cell lymphoma (DLL). Results: In five cases, FL and DLL cells were clonally related, as suggested by the identical MBR sequences, but in one case they were different. PCR single- strand conformation polymorphism (SSCP) and sequence analyses were performed for identification of structural alterations of the bcl-2 gene in the OFR region corresponding to the 239 amino acid p26-bcl-2a protein. In three of the six patients, a total of 11 point mutations of the ORF were detected in the DLL cells. Four of them, at positions 29, 46, 59, and 106, yielded amino acid replacements. Conclusions: These findings demonstrate that FL and DLL cells may be clonally related or unrelated. They also show that transformation of FL cells can be associated with somatic point mutations of the bcl-2 oncogene ORF sequence resulting in alteration of the p26-bcl-2a gene product.

KW - bcl-2 oncogene

KW - Diffuse large-cell lymphoma

KW - Follicular lymphoma

KW - Lymphoma transformation

KW - Somatic mutation

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M3 - Article

C2 - 9209654

AN - SCOPUS:0030749757

VL - 8

JO - Annals of Oncology

JF - Annals of Oncology

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