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Translocation remodeling in the primary BALB/c plasmacytoma TEPC 3610 †
Author(s) -
Kovalchuk Alexander L.,
Esa Arif,
Coleman Allen E.,
Park Sung S.,
Ried Thomas,
Cremer Christoph C.,
Janz Siegfried
Publication year - 2001
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/1098-2264(2000)9999:9999<::aid-gcc1094>3.0.co;2-i
Subject(s) - chromosomal translocation , biology , plasmacytoma , microbiology and biotechnology , gene , cancer research , genetics , multiple myeloma , immunology
Myc ‐activating chromosomal 12;15 translocations, the hallmark mutations of inflammation‐induced BALB/c plasmacytomas, have recently been shown to undergo remodeling by isotype switch‐like genetic recombinations that remove ∼ 180 kb of immunoglobulin heavy‐chain sequence in the vicinity of the rearranged, expressed Myc gene. Here we combine cytogenetic data on the 12;15 translocation (SKY and FISH) with the molecular analysis of key junction sites (long‐range PCR followed by DNA sequencing) to demonstrate that translocation remodeling occurred as an infrequent, stepwise, and disomic tumor progression event in the tetraploid, fully transformed, and transplantable plasmacytoma TEPC 3610. This result was used, in conjunction with previously obtained molecular data on five other primary plasmacytomas, to devise a hypothesis that predicts that the selective pressure to undergo translocation remodeling may be predetermined by the location of the break site in Myc . The pressure may be low if the break occurs 5′ of the normal promoter region of Myc , but it may be considerably stronger if the break occurs 3′ of the Myc promoter.Published 2001 Wiley‐Liss, Inc.