Journal article
Myc translocations in B cell and plasma cell neoplasms
DNA repair, Vol.5(9), pp.1213-1224
2006
DOI: 10.1016/j.dnarep.2006.05.017
PMID: 16815105
Abstract
Chromosomal translocations that join the cellular oncogene
Myc (c-
myc) with immunoglobulin (
Ig) heavy-chain (
Igh) or light-chain (
Igk,
Igl) loci are widely believed to be the crucial initiating oncogenic events in the development of B cell and plasma cell neoplasms in three mammalian species: Burkitt lymphoma (BL) in human beings, plasmacytoma (PCT) in mice, and immunocytoma in rats. Among the
Myc–
Ig translocations found in these neoplasms, mouse PCT T(12;15)(
Igh–
Myc) is of special interest because it affords a uniquely useful model system to study the fundamental outstanding questions on the mechanisms, genetics, and biological consequences of
Myc translocations. Mouse T(12;15) is the direct counterpart of the human BL t(8;14)(q24;q32) translocation and thus of great relevance for human cancer. Mouse T(12;15) is the only cancer-associated translocation in mice that occurs with high incidence, spontaneity, and cell-type specificity. Due to the development of PCR methods for the detection of the underlying reciprocal
Myc–
Igh junction fragments, it is now known that mouse T(12;15) can be a dynamic process that begins with the genetic exchange of
Myc and the
Igh switch μ region (
Sμ), progresses by class switch recombination (CSR) just 3′ of the translocation break site, and then undergoes further clonal diversification by micro-deletions in the junction flanks. The molecular pathway that subverts CSR to mediate
trans-chromosomal joining of
Myc and
Sμ (translocation origin) and secondary modification of
Myc–
Igh junctions (translocation “remodeling”) has not been elucidated, but recent evidence indicates that it includes CSR factors, such as the activation-induced cytidine deaminase (AID), that may also be involved in the ongoing neoplastic progression of the translocation-bearing tumor precursor. Transgenic mouse models of T(12;15)/t(8;14), including newly developed “iMyc” gene-insertion mice, will be useful in elucidating the role of these CSR factors in the progression of
Myc-induced B cell tumors.
Details
- Title: Subtitle
- Myc translocations in B cell and plasma cell neoplasms
- Creators
- Siegfried Janz - Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, NIH, Building 37, Room 3140A, Bethesda, MD 20892-4256, United States
- Resource Type
- Journal article
- Publication Details
- DNA repair, Vol.5(9), pp.1213-1224
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.dnarep.2006.05.017
- PMID
- 16815105
- ISSN
- 1568-7864
- eISSN
- 1568-7856
- Language
- English
- Date published
- 2006
- Academic Unit
- Pathology
- Record Identifier
- 9984083892002771
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