Transposition of the immunoglobulin heavy chain enhancer to the myc oncogene in a murine plasmacytoma

Abstract

A novel mechanism of oncogene activation by transposition of a tissue-specific cellular enhancer is described. A rearranged c-myc oncogene was cloned from murine plasmacytoma ABPC17 in the expectation that it would reflect the t(6;15) chromosome translocation carried by this tumor. The rearrangement instead reflects an insertion 361 bp 5' to the c-myc gene on chromosome 15. The insert conveys a 2.3 kb segment of the immunoglobulin heavy (H) chain locus from chromosome 12. Since the insertion introduces the lymphoid-specific enhancer from the JH-Smu region and also disrupts a region implicated in normal c-myc control, it may account for the c-myc transcription observed in ABPC17. The structure of the transposed segment and a corresponding deletion in the JH-Smu region suggests that the transposition reflects a complex recombination between chromosomes 15 and 12. Since the t(6;15) breakpoint is not near c-myc, chromosome 15 must have undergone an independent exchange with chromosome 6.