Follicular lymphoma with a novel t(14;18) breakpoint involving the immunoglobulin heavy chain switch mu region indicates an origin from germinal center B cells

Abstract With the use of DNA-fiber fluorescent in situ hybridization, a BCL2 protein positive follicular lymphoma with a novel BCL2 breakpoint involving the immunoglobulin heavy chain (IGH) switch mu (Sμ) region instead of the JH orDH gene segments was identified. Sequence analysis showed that the genomic breakpoint is localized between the Sμ region of the IGH complex and the first intron of BCL2. Reverse-transcriptase polymerase chain reaction showed expression of a unique hybrid IGH-BCL2 transcript involving the transcription initiation site Iμ. Sequence analysis of the VH region of the functional nontranslocatedIGH allele showed multiple shared somatic mutations but also a high intraclonal variation (53 differences in 15 clones), compatible with the lymphoma cells staying in or re-entering the germinal center. This is the first example of a t(14;18) translocation that results from an illegitimate IGH class-switch recombination during the germinal center B-cell stage.

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Evidence that in X-linked immunodeficiency with hyperimmunoglobulinemia M the intrinsic immunoglobulin heavy chain class switch mechanism is intact

European Journal of Immunology ◽

10.1002/eji.1830201212 ◽

1990 ◽

Vol 20 (12) ◽

pp. 2603-2608 ◽

Cited By ~ 36

Author(s):

Rudolf W. Hendriks ◽

Margriet E. M. Kraakman ◽

Ian W. Craig ◽

Teresa Espanol ◽

Ruud K. B. Schuurman

Keyword(s):

Heavy Chain ◽

Immunoglobulin Heavy Chain ◽

Class Switch ◽

Switch Mechanism

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Regulation of class switch recombination of the immunoglobulin heavy chain genes

Immunoglobulin Genes ◽

10.1016/b978-012053640-5/50014-8 ◽

1995 ◽

pp. 235-265 ◽

Cited By ~ 14

Author(s):

J. Zhang ◽

R.W. Alt ◽

T. Honjo

Keyword(s):

Heavy Chain ◽

Class Switch Recombination ◽

Immunoglobulin Heavy Chain ◽

Class Switch ◽

Immunoglobulin Heavy Chain Genes

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Pi, a pre-B-cell-specific enhancer element in the immunoglobulin heavy-chain enhancer

Molecular and Cellular Biology ◽

10.1128/mcb.13.10.5957-5969.1993 ◽

1993 ◽

Vol 13 (10) ◽

pp. 5957-5969

Author(s):

T A Libermann ◽

D Baltimore

Keyword(s):

B Cell ◽

Heavy Chain ◽

Mutational Analysis ◽

Protein S ◽

Immunoglobulin Heavy Chain ◽

Chain Gene ◽

Cell Stage ◽

Enhancer Activity ◽

Enhancer Element ◽

Light Chain Gene

We have identified a new immunoglobulin heavy-chain enhancer element, designated pi, between the microE2 and microE3 elements. The pi enhancer element is transcriptionally active primarily during early stages of B-cell development but becomes virtually inactive during B-cell maturation at about the stage of immunoglobulin kappa light-chain gene rearrangement. Mutational analysis suggests that the pi element is crucial for immunoglobulin heavy-chain enhancer activity at the pre-B-cell stage but is almost irrelevant for enhancer activity at the mature B-cell or plasma-cell stage. The activity of the pi enhancer element correlates with the presence of an apparently pre-B-cell-specific protein-DNA complex. The similarity of the pi site to recognition sequences for members of the ets gene family suggests that the protein(s) interacting with the pi site most likely are ets-related transcription factors.

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Characterization of mRNA transcripts and organization of human SP-A1 and SP-A2 genes

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1994.266.4.l354 ◽

1994 ◽

Vol 266 (4) ◽

pp. L354-L366 ◽

Cited By ~ 14

Author(s):

S. M. McCormick ◽

V. Boggaram ◽

C. R. Mendelson

Keyword(s):

Sequence Analysis ◽

Transcription Initiation ◽

Fetal Lung ◽

Surfactant Protein ◽

Companion Paper ◽

Initiation Site ◽

Oligonucleotide Primer ◽

Untranslated Sequence ◽

Mrna Transcripts ◽

Human Fetal Lung

In the present study, we have characterized the mRNA transcripts and intron-exon organization of the human surfactant protein (SP)A1 and SP-A2 genes. By primer extension analysis of mRNA isolated from human fetal lung explants using an oligonucleotide primer to exon II (as delineated in the SP-A1 gene), a minimum of nine primer extended transcripts was observed. Rapid amplification of cDNA ends was used to amplify the primer extended transcripts for sequence analysis. Sequence analysis of 47 full-length primer extended cDNAs and comparison with the sequences of the genes encoding SP-A1 and SP-A2 revealed four different classes of transcripts of the SP-A2 gene and five different classes of transcripts of the gene encoding SP-A1. A major difference between SP-A2 and SP-A1 mRNA transcripts is that SP-A2 transcripts are always comprised of sequences contained within six exons; the extra exon in SP-A2 (exon II of VI) encodes additional 5'-untranslated sequence and is located between exons I and II of SP-A1. By contrast, the majority of transcripts of the SP-A1 gene are comprised of sequences contained within five exons. In the cases of both SP-A1 and SP-A2 genes, a small proportion of the mRNA transcripts contain sequences present in alternate exons. In addition, the majority of the SP-A1 mRNA transcripts are initiated 5 bp downstream of the transcription initiation site of SP-A2. In our companion paper [McCormick and Mendelson. Am. J. Physiol. 266 (Lung Cell. Mol. Physiol. 10): L367-L374, 1994], we report that the SP-A1 and SP-A2 genes are differentially regulated during development and by adenosine 3',5'-cyclic monophosphate and glucocorticoids in human fetal lung in culture.

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Demonstration of Chimeric DNA of bcl-2 and Immunoglobulin Heavy Chain in Follicular Lymphoma and Subsequent Hodgkin Lymphoma from the Same Patient

Journal of Clinical and Experimental Hematopathology ◽

10.3960/jslrt.47.9 ◽

2007 ◽

Vol 47 (1) ◽

pp. 9-13 ◽

Cited By ~ 13

Author(s):

Naoya Nakamura ◽

Koichi Ohshima ◽

Masafumi Abe ◽

Yoshiyuki Osamura

Keyword(s):

Follicular Lymphoma ◽

Hodgkin Lymphoma ◽

Heavy Chain ◽

Immunoglobulin Heavy Chain

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Molecular features responsible for the absence of immunoglobulin heavy chain protein synthesis in an IgH− subgroup of multiple myeloma

Blood ◽

10.1182/blood.v96.3.1087 ◽

2000 ◽

Vol 96 (3) ◽

pp. 1087-1093 ◽

Cited By ~ 24

Author(s):

Tomasz Szczepański ◽

Mars B. van 't Veer ◽

Ingrid L. M. Wolvers-Tettero ◽

Anton W. Langerak ◽

Jacques J. M. van Dongen

Keyword(s):

Multiple Myeloma ◽

Heavy Chain ◽

Plasma Cells ◽

Somatic Hypermutation ◽

Immunoglobulin Heavy Chain ◽

Polymerase Chain Reaction Analysis ◽

Class Switch ◽

Molecular Features ◽

Igh Genes ◽

Polymerase Chain

Abstract This study involved 12 patients with multiple myeloma (MM), in whom malignant plasma cells did not contain immunoglobulin heavy chain (IgH) protein chains. Southern blot analysis revealed monoallelic Jh gene rearrangements in 10 patients, biallelic rearrangement in 1 patient, and biallelic deletion of the Jh and Cμ regions in 1 patient. Heteroduplex polymerase chain reaction analysis enabled the identification and sequencing of 9 clonal Jhgene rearrangements. Only 4 of the joinings were complete Vh-(D)-Jhrearrangements, including 3 in-frame rearrangements with evidence of somatic hypermutation. Five rearrangements concerned incomplete Dh-Jh joinings, mainly associated with deletion of the other allele. Curiously, in at least 1 of these 5 cases the second allele seemed to be in germline configuration, whereas the in-frame Vκ-Jκgene rearrangements contained somatic mutations. The configuration of the IGH genes was further investigated by use of Ch probes. In 5 patients the rearrangements in the Jh and Ch regions were not concordant, probably caused by illegitimate IGH class switch recombination (chromosomal translocations to 14q32.3). These data indicate that in many IgH− MM patients illegitimateIGH class switch rearrangement or illegitimate deletion of the functional Vh-(Dh)-Jhallele are responsible for IgH negativity. For example, the exclusive presence ofDh-Jhrearrangements in combination with mutated IGK genes can only be explained in terms of normal B-cell development, if the second (functional) IGH allele is deleted, which was probably the case in most patients. Therefore, defects at the DNA level are responsible for the lack of IgH protein production in most IgH− MM patients.

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