Common and variant gene fusions predict distinct clinical phenotypes in rhabdomyosarcoma.
OBJECTIVE
We evaluated the clinical features of the common PAX3-FKHR and variant PAX7-FKHR gene fusions observed in rhabdomyosarcoma.


METHODS
Reverse-transcriptase polymerase chain reaction (RT-PCR) assays were used to detect the gene fusions in 34 cases of rhabdomyosarcoma. Clinical data were obtained retrospectively and compared with the molecular results.


RESULTS
The PAX3-FKHR and PAX7-FKHR gene fusions were present in tumors from 18 and 16 patients, respectively. The group with a PAX7-FKHR fusion was younger (P = .01) and presented more often with an extremity lesion (82% v 22%; P = .001). PAX7-FKHR tumors were more often localized than PAX3-FKHR tumors (P = .03). In patients with metastatic disease at diagnosis, the patterns were different: PAX7-FKHR patients had metastatic disease that involved only bone (n = 2) and distant nodes (n = 2), while the PAX3-FKHR group had multiple sites involved, including bone (n = 7), marrow (n = 7), lungs (n = 3), distant nodes (n = 2), skin (n = 1), and brain (n = 1). No significant difference in relapse rate was observed. A trend toward improved overall survival in the PAX7-FKHR group was noted (P = .09). Event-free survival for this PAX7-FKHR group was significantly longer (P = .04).


CONCLUSIONS
Our results suggest that the common PAX3-FKHR and the variant PAX7-FKHR fusions are associated with distinct clinical phenotypes. Identification of fusion gene status may be a useful diagnostic tool in rhabdomyosarcoma.
Kelly
K M
KM
Division of Oncology, Children's Hospital of Philadelphia, PA, USA.
Womer
R B
RB
Sorensen
P H
PH
Xiong
Q B
QB
Barr
F G
FG
D000293:Adolescent; D000328:Adult; D001132:Arm; D002648:Child; D002675:Child, Preschool; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D006801:Humans; D007223:Infant; D007866:Leg; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D000072041:PAX3 Transcription Factor; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; D010641:Phenotype; D012008:Recurrence; D012189:Retrospective Studies; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics* / Q000473:pathology; D018233:Rhabdomyosarcoma, Embryonal / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse