Assessment of molecular genetic detection of chromosome translocations in the differential diagnosis of pediatric sarcomas.
BACKGROUND
Recent studies have shown that many types of soft-tissue sarcomas are characterized by specific chromosomal translocations, which are likely to be of etiologic significance. In order to evaluate their diagnostic impact, a panel of 129 sarcomas comprising 78 Ewing's tumors (ET), 19 rhabdomyosarcomas (RMS), 20 neuroblastomas (NB), 9 synovialsarcomas, 2 esthesioneuroblastomas, and 1 desmoplastic small-round-cell tumor (DSRCT) were analysed for the occurrence of the major recurrent translocations, such as t(11;22)(q24;q12), t(21;22)(q22;q12), t(11;22)(p13;q12), t(2;13)(q35;q14), t(1;13)(p36;q14), and t(X;18)(p11;q11).


METHODS
Nitrogen-frozen tissue material was analysed by means of Reverse Transcription followed by PCR (Polymerase-Chain Reaction) and nested PCR (RT-PCR). Specificity of the PCR products obtained was confirmed by non-isotopic Southern-Blot analysis with gene-specific probes and/or automated direct sequence analysis.


RESULTS
75 ETs have been shown to carry either a t(11;22) or t(21;22) translocation by identification of chimeric EWS-FLI-1 or EWS-ERG gene-fusion transcripts respectively. 3 ETs were lacking EWS/FLI-1 or EWS-ERG fusion products. 2 of these tumors were shown on review to have unusual morphological features for ETs. 8/19 RMS were initially diagnosed as alveolar RMS. These tumours were shown to carry either a t(2;13) translocation exhibiting chimeric PAX3-FKHR fusion transcripts or a t(1;13) translocation with PAX7-FKHR chimeric gene products. One RMS of the embryonal group also carried a t(1;13) translocation. Reevaluation demonstrated a partly alveolar morphology. In 8/9 synovial sarcomas a t(X;18) translocation was identified. Expression of a EWS-WTI gene-fusion product associated with a t(11;22) translocation was found in the DSRCT. None of these rearrangements were detected in the NBs and 2 esthesioneuroblastomas.


CONCLUSIONS
Our results support the concept that the major recurrent translocations are histogenetically specific for a subset of sarcomas. Thus, the detection of tumor type-specific translocations represents an extremely useful diagnostic modality as an adjunct to surgical pathology.
Dockhorn-Dworniczak
B
B
Gerhard-Domagk-Institut für Pathologie, Münster.
Schäfer
K L
KL
Blasius
S
S
Christiansen
H
H
Koscielniak
E
E
Ritter
J
J
Winkelmann
W
W
Jürgens
H
H
Böcker
W
W
D001483:Base Sequence / Q000235:genetics; D002648:Child; D002874:Chromosome Mapping; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008967:Molecular Biology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012509:Sarcoma / Q000175:diagnosis* / Q000235:genetics; D012983:Soft Tissue Neoplasms / Q000175:diagnosis* / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics*
D005819:Genetic Markers