1. Complex biallelicIGH rearrangements in IgM-expressing Z-138 cell line: Involvement of downstream immunoglobulin class switch recombination
- Author
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Zeev Estrov, Antoinette A. T. P. Brink, James A. L. Fenton, K Kleiverda, Anton K. Raap, Ed Schuuring, Conny de Boer, Philip M. Kluin, Jeroen E. J. Guikema, Other departments, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Stem Cell Aging Leukemia and Lymphoma (SALL), and Targeted Gynaecologic Oncology (TARGON)
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Cancer Research ,Molecular Sequence Data ,Somatic hypermutation ,chemical and pharmacologic phenomena ,Biology ,Translocation, Genetic ,Immunoglobulin Class Switch Recombination ,Cell Line ,REGION ,CYTIDINE DEAMINASE AID ,GENETIC-ANALYSIS ,immune system diseases ,MULTIPLE-MYELOMA ,hemic and lymphatic diseases ,SOMATIC HYPERMUTATION ,LYMPHOMA ,Genetics ,Humans ,3' Flanking Region ,Allele ,Enhancer ,Lymphoma, Follicular ,Alleles ,Chromosomes, Human, Pair 14 ,Gene Rearrangement ,CHROMOSOMAL TRANSLOCATION ,Base Sequence ,Genes, Immunoglobulin ,CHRONIC LYMPHOCYTIC-LEUKEMIA ,Breakpoint ,DNA ,Gene rearrangement ,IN-SITU HYBRIDIZATION ,Immunoglobulin Class Switching ,Molecular biology ,Immunoglobulin M ,Immunoglobulin class switching ,Immunoglobulin heavy chain ,Immunoglobulin Heavy Chains ,Chromosomes, Human, Pair 8 - Abstract
Chromosomal translocations involving the immunoglobulin (Ig) receptor loci usually disrupt and silence these loci. On the basis of observations in follicular lymphoma (FL) with downstream Ig heavy chain (IGH) class switch recombination (CSR), we hypothesized that downstream CSR-mediated chromosomal translocations would leave the V(D)J-Cmu transcription unit intact, thereby still allowing IgM expression from the IGH allele involved in the translocation. To test this hypothesis, we analyzed biallelic IGH translocations in the IgM-expressing cell line Z-138 by interphase FISH, DNA fiber-FISH, long-distance vectorette PCR, and DNA sequencing. One IGH allele was involved in a t(11;14), showing a break in the JH region that juxtaposed the El,L enhancer and the 3' Calpha enhancers to the cyclin D1 gene. The other IGH allele contained a t(8; 14) breakpoint involving the 3' end of a Sgamma region, whereas the reciprocal breakpoint at 8q24 was approximately 40 kb centromeric of MYC. Molecular analysis showed that this IGH allele harbored a normal V(D)J-Cmu complex, which is responsible for IgM expression. These data show that chromosomal breakpoints such as the t(8; 14) can occur in downstream IGH constant regions and do not necessarily interfere with Ig expression. (C) 2004 Wiley-Liss, Inc.
- Published
- 2005
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