Abstract
Pediatric undifferentiated soft tissue sarcomas (USTS) are a diagnostically challenging
group of neoplasms. Recently, a subcategory of USTS with primitive round cell morphology
and a t(4;19)(q35;q13) rearrangement has been defined. The present study applied high-throughput
array comparative genomic hybridization together with spectral karyotyping, four-color
fluorescence in situ hybridization (FISH), and reverse transcriptase–polymerase chain
reaction (RT-PCR) to a series of three pediatric USTS. Two of these had primitive
round cell morphology with CD99 positivity; the third had a spindled and myxoid appearance.
By genomic analyses, both primitive round cell sarcomas had t(4;19)(q13;q35) rearrangements
in addition to several imbalances throughout the genome. Four-color FISH and in silico
analyses of the breakpoint region at 19q13 identified the potential involvement of
the candidate oncogene CIC. By RT-PCR, fusion transcripts involving CIC (19q13) and DUX4 (4q35) were confirmed to be present in both primitive round cell sarcomas, further
defining the breakpoints seen by genomic analysis. Described here are two tumors belonging
to the rare category of CIC–DUX4-positive primitive sarcomas, with detailed cytogenetic and genomic information regarding
this novel subclass of pediatric malignancy. Molecular and cytogenetic techniques
for the detection of the CIC–DUX4 fusion gene are described, to aid in recognition and diagnosis.
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Article info
Publication history
Accepted:
June 17,
2009
Received:
June 1,
2009
Identification
Copyright
© 2009 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
