Insertion of excised IgH switch sequences causes overexpression of cyclin D1 in a myeloma tumor cell

Ana Gabrea; P. Leif Bergsagel; Marta Chesi; Yaping Shou; W. Michael Kuehl

doi:10.1016/S1097-2765(00)80180-X

Insertion of excised IgH switch sequences causes overexpression of cyclin D1 in a myeloma tumor cell

Ana Gabrea, P. Leif Bergsagel, Marta Chesi, Yaping Shou, W. Michael Kuehl

Hematology/Oncology

Research output: Contribution to journal › Article › peer-review

82 Scopus citations

Abstract

Oncogenes are often dysregulated in B cell tumors as a result of a reciprocal translocation involving an immunoglobulin locus. The translocations are caused by errors in two developmentally regulated DNA recombination processes: V(D)J and IgH switch recombination. Both processes share the property of joining discontinuous sequences from one chromosome and releasing intervening sequences as circles that are lost from progeny cells. Here we show that these intervening sequences may instead insert in the genome and that during productive IgH mu-epsilon switch recombination in U266 myeloma tumor cells, a portion of the excised IgH switch intervening sequences containing the 3' α-1 enhancer has inserted on chromosome 11q13, resulting in overexpression of the adjacent cyclin D1 oncogene.

Original language	English (US)
Pages (from-to)	119-123
Number of pages	5
Journal	Molecular Cell
Volume	3
Issue number	1
DOIs	https://doi.org/10.1016/S1097-2765(00)80180-X
State	Published - Jan 1999

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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title = "Insertion of excised IgH switch sequences causes overexpression of cyclin D1 in a myeloma tumor cell",

abstract = "Oncogenes are often dysregulated in B cell tumors as a result of a reciprocal translocation involving an immunoglobulin locus. The translocations are caused by errors in two developmentally regulated DNA recombination processes: V(D)J and IgH switch recombination. Both processes share the property of joining discontinuous sequences from one chromosome and releasing intervening sequences as circles that are lost from progeny cells. Here we show that these intervening sequences may instead insert in the genome and that during productive IgH mu-epsilon switch recombination in U266 myeloma tumor cells, a portion of the excised IgH switch intervening sequences containing the 3' α-1 enhancer has inserted on chromosome 11q13, resulting in overexpression of the adjacent cyclin D1 oncogene.",

author = "Ana Gabrea and Bergsagel, {P. Leif} and Marta Chesi and Yaping Shou and Kuehl, {W. Michael}",

note = "Funding Information: We are indebted to Drs. A. Roschke and I. R. Kirsch for aiding us in the FISH analyses. We also thank Drs. E. Max and F. Mills for providing probes and for insightful comments. This work was supported by the Howard Temin Award from the National Cancer Institute (CA74265) to P. L. B. ",

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T1 - Insertion of excised IgH switch sequences causes overexpression of cyclin D1 in a myeloma tumor cell

AU - Gabrea, Ana

AU - Bergsagel, P. Leif

AU - Chesi, Marta

AU - Shou, Yaping

AU - Kuehl, W. Michael

N1 - Funding Information: We are indebted to Drs. A. Roschke and I. R. Kirsch for aiding us in the FISH analyses. We also thank Drs. E. Max and F. Mills for providing probes and for insightful comments. This work was supported by the Howard Temin Award from the National Cancer Institute (CA74265) to P. L. B.

PY - 1999/1

Y1 - 1999/1

N2 - Oncogenes are often dysregulated in B cell tumors as a result of a reciprocal translocation involving an immunoglobulin locus. The translocations are caused by errors in two developmentally regulated DNA recombination processes: V(D)J and IgH switch recombination. Both processes share the property of joining discontinuous sequences from one chromosome and releasing intervening sequences as circles that are lost from progeny cells. Here we show that these intervening sequences may instead insert in the genome and that during productive IgH mu-epsilon switch recombination in U266 myeloma tumor cells, a portion of the excised IgH switch intervening sequences containing the 3' α-1 enhancer has inserted on chromosome 11q13, resulting in overexpression of the adjacent cyclin D1 oncogene.

AB - Oncogenes are often dysregulated in B cell tumors as a result of a reciprocal translocation involving an immunoglobulin locus. The translocations are caused by errors in two developmentally regulated DNA recombination processes: V(D)J and IgH switch recombination. Both processes share the property of joining discontinuous sequences from one chromosome and releasing intervening sequences as circles that are lost from progeny cells. Here we show that these intervening sequences may instead insert in the genome and that during productive IgH mu-epsilon switch recombination in U266 myeloma tumor cells, a portion of the excised IgH switch intervening sequences containing the 3' α-1 enhancer has inserted on chromosome 11q13, resulting in overexpression of the adjacent cyclin D1 oncogene.

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Insertion of excised IgH switch sequences causes overexpression of cyclin D1 in a myeloma tumor cell

Abstract

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