Myc oncogene activation in B and T lymphoid tumours

Abstract

The chromosome translocations characteristic of certain B lymphoid tumours associate the myc oncogene and immunoglobulin loci. The typical t(12;15) in murine plasmacytomas and analogous t(14;8) in Burkitt lyphomas couple the myc coding region to one of the switch recombination regions within the immunoglobulin heavy (H) chain locus; hence the switch machinery may promote some translocations. Significantly, translocation induces constitutive myc expression, the untranslocated myc allele remaining silent. The predilection for breakpoints near the 5´ end of the c -myc gene may reflect selection for altered myc regulation. In most tumours, the stimulatory effect of the H locus context is not understood, but an H locus enhancer participates in some tumours, including one displaying a novel transposition . The variant (6;15) translocations found in about 15 % of plasmacytomas involve the myc band and the region of chromosome 6 where the k locus lies. The t(6;15) is shown here to represent an exchange between C K and a chromosome 15 locus (designated pvt -1) which lies unexpectedly far from c-myc .The association of myc expression with pvt -1 alterations suggest that myc can be activated at a distance. Myc has also been implicated in some T lymphomas by detection of proviral inserts near myc and also surprisingly, within the pvt -1 locus. Inserts near myc appear to activate its expression via the retroviral enhancer.