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Previously hidden chromosome aberrations in T(12;15)-positive BALB/c plasmacytomas uncovered by multicolor spectral karyotyping. Cancer Res 1997 Oct 15;57(20):4585-92

Date

10/23/1997

Pubmed ID

9377573

Abstract

The majority of BALB/c mouse plasmacytomas harbor a balanced T(12;15) chromosomal translocation deregulating the expression of the proto-oncogene c-myc. Recent evidence suggests that the T(12;15) is an initiating tumorigenic mutation that occurs in early plasmacytoma precursor cells. However, the possible contribution of additional chromosomal aberrations to the progression of plasmacytoma development has been largely ignored. Here we use multicolor spectral karyotyping (SKY) to evaluate 10 established BALB/c plasmacytomas in which the T(12;15) had been previously detected by G banding. SKY readily confirmed the presence of this translocation in all of these tumors and in three plasmacytomas newly identified secondary cytogenetic changes of the c-myc-deregulating chromosome (Chr) T(12;15). In addition, numerous previously unknown aberrations were found to be scattered throughout the genome, which was interpreted to reflect the general genomic instability of plasmacytomas. Instability of this sort was not uniform, however, because only half of the tumors were heavily rearranged. Seven apparent hot spots of chromosomal rearrangements (40% incidence) were identified and mapped to Chrs 1B, 1G-H, 2G-H1, 4C7-D2, 12D, 14C-D2, and XE-F1. Two of these regions, Chr 1B and Chr 4C7-D2, are suspected to harbor plasmacytoma susceptibility loci; Pctr1 and Pctr2 on Chr 4C7-D2 and as yet unnamed loci on Chr 1B. These results suggest that secondary chromosomal rearrangements contribute to plasmacytoma progression in BALB/c mice. To evaluate the biological significance of these rearrangements, SKY will be used in follow-up experiments to search for the presence of recurrent and/or consistent secondary cytogenetic aberrations in primary BALB/c plasmacytomas.

Author List

Coleman AE, Schröck E, Weaver Z, du Manoir S, Yang F, Ferguson-Smith MA, Ried T, 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 Aberrations
Chromosome Mapping
Genes, myc
Genetic Markers
Karyotyping
Metaphase
Mice
Mice, Inbred BALB C
Plasmacytoma
Translocation, Genetic
jenkins-FCD Prod-399 190a069c593fb5498b7fcd942f44b7bc9cdc7ea1