Molecular assays for chromosomal translocations in the diagnosis of pediatric soft tissue sarcomas.
OBJECTIVE
To compare molecular assays for characteristic chromosomal translocations with standard histopathologic and cytogenetic analysis in the differential diagnosis of pediatric soft tissue sarcomas.


METHODS
Blinded comparison with histopathologic diagnosis.


METHODS
Tertiary care children's hospital.


METHODS
A total of 79 soft tissue sarcoma patients with frozen tumor tissue and histopathologic slides available for review.


METHODS
The RNA from the tumors was assayed by the reverse transcriptase-polymerase chain reaction. These assays detect PAX3-FKHR and PAX7-FKHR chimeric transcripts in alveolar rhabdomyosarcoma, EWS-FLI1 and EWS-ERG chimeric transcripts in Ewing's sarcoma, and EWS-WT1 chimeric transcripts in desmoplastic small round cell tumor.


METHODS
The polymerase chain reaction findings were compared with cytogenetic and histopathologic results.


RESULTS
These assays detected chimeric transcripts in all cases in which translocations were found by standard cytogenetics as well as additional cases without cytogenetically detectable translocations. PAX3-FKHR or PAX7-FKHR fusions were present in 18 of 21 alveolar rhabdomyosarcomas, two of 30 embryonal rhabdomyosarcomas, and one of seven undifferentiated sarcomas. EWS-FLI1 or EWS-ERG fusions were detected in six of eight Ewing's sarcomas and one of seven undifferentiated sarcomas. The EWS-WT1 fusion was found in three of three desmoplastic small round cell tumors.


CONCLUSIONS
Molecular assays for specific gene fusions provide a genetic approach to the differential diagnosis of soft tissue sarcomas. The genetic categories correspond closely to the standard histopathologic categories. The polymerase chain reaction assays for chimeric transcripts are useful tools for the rapid and objective assessment of pediatric soft tissue sarcomas.
Barr
F G
FG
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6082.
Chatten
J
J
D'Cruz
C M
CM
Wilson
A E
AE
Nauta
L E
LE
Nycum
L M
LM
Biegel
J A
JA
Womer
R B
RB
D001483:Base Sequence; D002648:Child; D004268:DNA-Binding Proteins; D003937:Diagnosis, Differential; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000032:analysis; D012194:RNA-Directed DNA Polymerase; D011993:Recombinant Fusion Proteins; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000473:pathology; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology*; D012512:Sarcoma, Ewing / Q000235:genetics / Q000473:pathology; D018228:Sarcoma, Small Cell / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors; D014178:Translocation, Genetic / Q000235:genetics*
D004268:DNA-Binding Proteins; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D012194:RNA-Directed DNA Polymerase