Linked Life Data

11245476

Source:http://linkedlifedata.com/resource/pubmed/id/11245476

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-3-13
pubmed:abstractText
The t(11;14)(q13;q32) between the BCL-1 and immunoglobulin heavy chain gene (IgH) loci in mantle cell lymphoma (MCL) are believed to be mediated by the mechanism of V(D)J recombination similar to the t(14; 18) in follicular lymphoma (FL). We have recently shown that the t(14;18) event creates staggered double-strand breaks in the BCL-2 locus, and that the t(14;18) junctions contain templated nucleotide insertions (T-nucleotides; U. Jäger et al., Blood, 95: 3520-3529, 2000). Reasoning that the earlier (pregerminal center) B-cell origin of MCL might be reflected in a different molecular structure of the chromosomal breakpoints, we PCR-amplified diagnostic samples from 93 patients. Thirty-six samples (39%) were positive for the direct (BCL-1/J(H)) and 23 for both direct and reciprocal (D(H)/BCL-1) junctions. The breaks on chromosome 14 exhibited features of V(D)J-mediated recombination as shown by D(H) and J(H) coding end processing. However, duplications of BCL-1 sequences in 39% of the 23 patients indicate staggered double-strand breaks in the major translocation cluster region (MTC). This is incompatible with V(D)J recombination and indicates a different mechanism of cleavage. The use of J(H)6 in the junctions (39%) was similar to that in the immunoglobulin genes of normal B cells and B-CLL, but considerably less than in FL. Only 2 of 36 samples contained a BCL-1/DJ(H) rearrangement, which was indicative of a previous DJ(H) rearrangement. Most importantly, 19% of the BCL-1/IgH junctions with inserts of > or =5 nucleotides contained error-prone copies (T-nucleotides) of 8-12 nucleotides originating from the surrounding BCL-1 or IgH regions, a lower rate than in FL. No correlation was found between the addition of T-nucleotides and the rate of somatic mutation in the immunoglobulin genes. We conclude that the t(11;14) and t(14;18) use the same basic mechanism of translocation including V(D)J-mediated recombination, double-strand staggered breaks, and template-dependent, error-prone DNA-synthesis. However, the distinct differences in the utilization of J(H) regions suggest that the t(11;14) occurs predominantly during an attempted primary D(H)-J(H) rearrangement in early B cells, whereas the t(14;18) mostly occurs during secondary rearrangement. This is in agreement with the pregerminal center B-cell origin of MCL.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1629-36
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11245476-Base Sequence, pubmed-meshheading:11245476-Chromosome Breakage, pubmed-meshheading:11245476-Chromosomes, Human, Pair 11, pubmed-meshheading:11245476-Chromosomes, Human, Pair 14, pubmed-meshheading:11245476-DNA Transposable Elements, pubmed-meshheading:11245476-Gene Rearrangement, B-Lymphocyte, Heavy Chain, pubmed-meshheading:11245476-Genes, Immunoglobulin, pubmed-meshheading:11245476-Genes, bcl-1, pubmed-meshheading:11245476-Humans, pubmed-meshheading:11245476-Immunoglobulin Heavy Chains, pubmed-meshheading:11245476-Immunoglobulin Idiotypes, pubmed-meshheading:11245476-Immunoglobulin J-Chains, pubmed-meshheading:11245476-Lymphoma, Mantle-Cell, pubmed-meshheading:11245476-Molecular Sequence Data, pubmed-meshheading:11245476-Polymerase Chain Reaction, pubmed-meshheading:11245476-Templates, Genetic, pubmed-meshheading:11245476-Translocation, Genetic
pubmed:year
2001
pubmed:articleTitle
Templated nucleotide addition and immunoglobulin JH-gene utilization in t(11;14) junctions: implications for the mechanism of translocation and the origin of mantle cell lymphoma.
pubmed:affiliation
Department of Internal Medicine, University of Vienna, Austria.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't