Faculty Collaboration Database

Myc translocations in B cell and plasma cell neoplasms. DNA Repair (Amst) 2006 Sep 08;5(9-10):1213-24

Date

07/04/2006

Pubmed ID

16815105

DOI

10.1016/j.dnarep.2006.05.017

Scopus ID

2-s2.0-33747893961 (requires institutional sign-in at Scopus site)   85 Citations

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 mu region (Smu), 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 Smu (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.

Author List

Janz S

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Chromosome Breakage
Disease Models, Animal
Genes, Immunoglobulin Heavy Chain
Genes, myc
Humans
Immunoglobulin Class Switching
Lymphoma, B-Cell
Mice
Mice, Inbred BALB C
Mice, Transgenic
Models, Genetic
Plasmacytoma
Polymerase Chain Reaction
Translocation, Genetic