Structural analysis of PAX7 rearrangements in alveolar rhabdomyosarcoma

In the pediatric cancer alveolar rhabdomyosarcoma, the common 2;13 and less frequent 1;13 translocations fuse PAX3 and PAX7, respectively: with FKHR t o produce chimeric genes. To compare structural features of these rearrange ments, Mle cloned and mapped a 64-kb genomic region containing PAX7 exons 5 through 8. With the use of Southern blot methodology, rearrangements of th e 30-kb PAX7 intron 7 were detected in 9 of 9 PAX7-FKHR-positive cases. Sim ilar to our t(2;13) studies, the t(1;13) breakpoints were randomly distribu ted within the seventh intron. In contrast with the >90% frequency of recip rocal rearrangements in the t(2;13), reciprocal rearrangements involving th e 3' PAX7 region were detected in only 4 of 9 cases. Furthermore, we detect ed PAX7-FKHR genomic amplification in 10 of 11 cases, in contrast with the <5% frequency of PAX3-FKHR amplification. The differences in occurrence, re ciprocity, and amplification between the PAX3-FKHR and PAX7-FKHR fusions in dicate important differences in the mechanism of the two associated chromos omal translocation events. (C) Elsevier Science Inc., 2000. All rights rese rved.