title: Structural analysis of PAX7 rearrangements in alveolar rhabdomyosarcoma.
abstract: In the pediatric cancer alveolar rhabdomyosarcoma, the common 2;13 and less frequent 1;13 translocations fuse PAX3 and PAX7, respectively, with FKHR to produce chimeric genes. To compare structural features of these rearrangements, we cloned and mapped a 64-kb genomic region containing PAX7 exons 5 through 8. With the use of Southern blot methodology, rearrangements of the 30-kb PAX7 intron 7 were detected in 9 of 9 PAX7-FKHR-positive cases. Similar to our t(2;13) studies, the t(1;13) breakpoints were randomly distributed within the seventh intron. In contrast with the > 90% frequency of reciprocal rearrangements in the t(2;13), reciprocal rearrangements involving the 3' PAX7 region were detected in only 4 of 9 cases. Furthermore, we detected PAX7-FKHR genomic amplification in 10 of 11 cases, in contrast with the < 5% frequency of PAX3-FKHR amplification. The differences in occurrence, reciprocity, and amplification between the PAX3-FKHR and PAX7-FKHR fusions indicate important differences in the mechanism of the two associated chromosomal translocation events.
authors.affiliation: Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia 19104-6082, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Fitzgerald
authors.forename: A M
authors.initials: AM
authors.lastname: Scherr
authors.forename: F G
authors.initials: FG
authors.lastname: Barr
mesh_terms: D002648:Child; D002878:Chromosomes, Human, Pair 1; D002882:Chromosomes, Human, Pair 13; D004268:DNA-Binding Proteins / Q000235:genetics; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D051763:PAX7 Transcription Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D004268:DNA-Binding Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human; D014157:Transcription Factors