Genomic characterization of the chromosomal breakpoints of t(4;14) of multiple myeloma suggests more than one possible aetiological mechanism.

2.50
Hdl Handle:
http://hdl.handle.net/10541/82375
Title:
Genomic characterization of the chromosomal breakpoints of t(4;14) of multiple myeloma suggests more than one possible aetiological mechanism.
Authors:
Fenton, James A L; Pratt, Guy; Rawstron, Andy C; Sibley, Kathryn; Rothwell, Dominic G; Yates, Zoe; Dring, Ann; Richards, Steve J; Ashcroft, A John; Davies, Faith E; Owen, Roger G; Child, J Anthony; Morgan, Gareth J
Abstract:
Using FISH-based techniques, rearrangements of the immunoglobulin heavy-chain (IgH) locus at 14q32 have been found in the majority of cases of multiple myeloma (MM). Some of these IgH translocations are recurrent and we have characterized the genomic breakpoints of seven t(4;14) translocations from MM patients, using a combination of vectorette and conventional polymerase chain reaction methods, the aim being to understand the molecular mechanism leading to MM. Conventionally, the chromosome 14q32 breakpoints in these reciprocal translocations are believed to be located in the IgH mu switch (S) region and a further downstream S region with deletion of intervening DNA occurring as a result of aberrant class switch recombination (CSR); this was seen in five of the cases analysed. However, in two patients it was possible to demonstrate that the rearranged hybrid switch region sequence was joined to DNA from chromosome 4p16, suggesting that IgH translocations can occur in B cells that have already undergone legitimate CSR. The complex nature of these rearrangements leads us to speculate that primary IgH translocations may occur at different time points in the development in MM plasma cells, either at the time of physiological CSR or at a later stage, possibly involving a different mechanism.
Affiliation:
Academic Unit of Haematology and Oncology, Algernon Firth Building, University of Leeds, LEEDS LS2 9JT, UK. jamesf@lrf.leeds.ac.uk
Citation:
Genomic characterization of the chromosomal breakpoints of t(4;14) of multiple myeloma suggests more than one possible aetiological mechanism. 2003, 22 (7):1103-13 Oncogene
Journal:
Oncogene
Issue Date:
20-Feb-2003
URI:
http://hdl.handle.net/10541/82375
DOI:
10.1038/sj.onc.1206335
PubMed ID:
12592397
Type:
Article
Language:
en
ISSN:
0950-9232
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorFenton, James A L-
dc.contributor.authorPratt, Guy-
dc.contributor.authorRawstron, Andy C-
dc.contributor.authorSibley, Kathryn-
dc.contributor.authorRothwell, Dominic G-
dc.contributor.authorYates, Zoe-
dc.contributor.authorDring, Ann-
dc.contributor.authorRichards, Steve J-
dc.contributor.authorAshcroft, A John-
dc.contributor.authorDavies, Faith E-
dc.contributor.authorOwen, Roger G-
dc.contributor.authorChild, J Anthony-
dc.contributor.authorMorgan, Gareth J-
dc.date.accessioned2009-09-23T14:50:15Z-
dc.date.available2009-09-23T14:50:15Z-
dc.date.issued2003-02-20-
dc.identifier.citationGenomic characterization of the chromosomal breakpoints of t(4;14) of multiple myeloma suggests more than one possible aetiological mechanism. 2003, 22 (7):1103-13 Oncogeneen
dc.identifier.issn0950-9232-
dc.identifier.pmid12592397-
dc.identifier.doi10.1038/sj.onc.1206335-
dc.identifier.urihttp://hdl.handle.net/10541/82375-
dc.description.abstractUsing FISH-based techniques, rearrangements of the immunoglobulin heavy-chain (IgH) locus at 14q32 have been found in the majority of cases of multiple myeloma (MM). Some of these IgH translocations are recurrent and we have characterized the genomic breakpoints of seven t(4;14) translocations from MM patients, using a combination of vectorette and conventional polymerase chain reaction methods, the aim being to understand the molecular mechanism leading to MM. Conventionally, the chromosome 14q32 breakpoints in these reciprocal translocations are believed to be located in the IgH mu switch (S) region and a further downstream S region with deletion of intervening DNA occurring as a result of aberrant class switch recombination (CSR); this was seen in five of the cases analysed. However, in two patients it was possible to demonstrate that the rearranged hybrid switch region sequence was joined to DNA from chromosome 4p16, suggesting that IgH translocations can occur in B cells that have already undergone legitimate CSR. The complex nature of these rearrangements leads us to speculate that primary IgH translocations may occur at different time points in the development in MM plasma cells, either at the time of physiological CSR or at a later stage, possibly involving a different mechanism.en
dc.language.isoenen
dc.subjectCancer Stem Cells-
dc.subject.meshB-Lymphocytes-
dc.subject.meshBase Sequence-
dc.subject.meshCell Transformation, Neoplastic-
dc.subject.meshChromosome Breakage-
dc.subject.meshChromosomes, Human, Pair 14-
dc.subject.meshChromosomes, Human, Pair 4-
dc.subject.meshClone Cells-
dc.subject.meshGene Rearrangement, B-Lymphocyte, Heavy Chain-
dc.subject.meshGenes, Immunoglobulin-
dc.subject.meshGenes, Switch-
dc.subject.meshHumans-
dc.subject.meshImmunoglobulin Class Switching-
dc.subject.meshImmunoglobulin Switch Region-
dc.subject.meshImmunoglobulin mu-Chains-
dc.subject.meshModels, Biological-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshMultiple Myeloma-
dc.subject.meshNeoplastic Stem Cells-
dc.subject.meshPolymerase Chain Reaction-
dc.subject.meshSequence Alignment-
dc.subject.meshSequence Homology, Nucleic Acid-
dc.subject.meshTranslocation, Genetic-
dc.titleGenomic characterization of the chromosomal breakpoints of t(4;14) of multiple myeloma suggests more than one possible aetiological mechanism.en
dc.typeArticleen
dc.contributor.departmentAcademic Unit of Haematology and Oncology, Algernon Firth Building, University of Leeds, LEEDS LS2 9JT, UK. jamesf@lrf.leeds.ac.uken
dc.identifier.journalOncogeneen

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