Novel formation and amplification of the PAX7-FKHR fusion gene in a case of alveolar rhabdomyosarcoma.
Alveolar rhabdomyosarcomas frequently exhibit specific translocations, resulting in the fusion of the FKHR gene at 13q14 with either the PAX3 or PAX7 gene at 2q35 and 1p36, respectively. Comparative genomic hybridization revealed amplification at 13q14 and 1p36, suggesting amplification of the PAX7-FKHR fusion gene in two cases of alveolar rhabdomyosarcoma. A PAX7-FKHR fusion transcript was demonstrated in both cases by reverse transcription-polymerase chain reaction followed by sequence analysis. In one case, amplification of the PAX7 gene and 3'-and 5'-FKHR gene sequences was demonstrated by using interphase fluorescence in situ hybridization on tumor imprints. The colocalization, variable copy number, and distribution of signals from the three cosmids was consistent with amplification of these sequences on double minutes, which were present cytogenetically. Chromatin release studies suggested that the amplified sequences correlated with amplification of the PAX7-FKHR fusion gene which resulted from the insertion of PAX7 sequences into the first intron of FKHR gene, in keeping with the absence of cytogenetic evidence for derivative chromosomes.
Section of Paediatrics, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
S
S
Weber-Hall
A
A
McManus
J
J
Anderson
T
T
Nojima
S
S
Abe
K
K
Pritchard-Jones
J
J
Shipley
D002648:Child; D002675:Child, Preschool; D002843:Chromatin / Q000378:metabolism; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1; D002882:Chromosomes, Human, Pair 13; D002889:Chromosomes, Human, Pair 2; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D051763:PAX7 Transcription Factor; D016133:Polymerase Chain Reaction; D011123:Polyploidy; D012194:RNA-Directed DNA Polymerase; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics*; D017421:Sequence Analysis; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
D002843:Chromatin; 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; D012194:RNA-Directed DNA Polymerase