Deletional remodeling of c-myc-deregulating chromosomal translocations

Evidence is presented for the existence of a novel remodeling-by-deletion mechanism that alters the fine structure of c-myc-deregulating chromosomal translocations in t(12;15)-positive BALB/c plasmacytomas. DNA sequence analysis of the t(12;15) in five primary tumors revealed the co-existence of precursor cells harboring genetic recombinations between the immunoglobulin heavy-chain mu locus (Igh mu) and c-myc with clonally related progenitors containing rearrangements between the immunoglobulin heavy-chain alpha locus (Igh alpha) and c-myc. Clonal relatedness was based upon unique junction fragments between the switch region of Igh mu and c-myc. S mu/c-myc junctions are thus useful clonotypic markers for monitoring the conversion of Igh mu/c-myc-positive tumor precursor clones into Igh alpha/c-myc-positive plasmacytomas. Aberrant isotype switch recombination appears to be the most likely mechanism effecting this conversion event (other possibilities are discussed) which may help to explain the preferred usage of the Igh alpha locus in recombinations with c-myc in t(12;15)-positive plasma cell tumors in BALB/c mice.