[89] Translocations 12;16 and 12;22 in Pediatric Myxoid/Round Cell Liposarcoma; Prevalence and Distribution

R Streblow, K Perry, M Miettinen, R Alaggio, CM Coffin, AL Folpe, M Nelson, A Dafferner, J Woodard, K Yeh, JA Bridge. University of Nebraska Medical Center, Omaha, NE; AFIP, Washington, DC; University of Padova, Italy; Vanderbilt University, Nashville, TN; Mayo Clinic, Rochester, MN

Background: Myxoid/round cell liposarcomas (MLPS) are characterized by FUS-DDIT3 [t(12;16)(q13;p11)] or EWSR1-DDIT3 [t(12;22)(q13;q12)] fusions. MLPS arise chiefly in adults 40-60 yrs of age. Within this population, the t(12;16) is present in >90% of MLPS and the t(12;22) in <5%. As a diagnostic aid, and to determine the prevalence/distribution of these translocations in pediatric MLPS, we constructed FISH probe sets that can: 1) be performed on formalin-fixed, paraffin-embedded tissue; and 2) identify potential unusual variant translocations or cryptic rearrangements.
Design: Unstained tissue sections from 62 children/young adults (<22 yrs of age) to include 50 MLPS, 7 pleomorphic MLPS, 1 spindle cell MLPS, 1 pleomorphic LPS, 1 lipoblastoma, 1 atypical lipomatous tumor (ALT), and 1 low grade fibromyxoid sarcoma (LGFMS) were submitted for molecular cytogenetic analysis with the diagnoses blinded to the FISH laboratory. Bicolor FISH was performed on each specimen using commercial and/or custom-designed probes composed of select BAC/cosmid clone cocktails capable of assessing DDIT3, FUS and EWSR1 loci independently or as fused translocations.
Results: A FUS-DDIT3 fusion was observed in 37 (86%) of the 43 fusion positive MLPS and an EWSR1-DDIT3 in 6 (14%). Of note, 2 cases exhibited insertions that were not detectable with the commercially available break apart probes of the insertion recipient loci and could only be accurately classified using the custom-designed spanning probes. Also, 1 case demonstrated a rearrangement of only the DDIT3 locus (suggesting the presence of a DDIT3 variant translocation). Seven MLPS, the pleomorphic and spindle cell MLPS, the pleomorphic LPS, the lipoblastoma and the ALT were negative for rearrangements of FUS, DDIT3 and EWSR1. The LGFMS was positive for a FUS-CREB3L2 fusion.
Conclusions: FISH analysis with these newly designed probe sets is a reliable and specific method of detecting MLPS-associated fusions in routinely processed tissue and it may serve as a diagnostic aid in distinguishing MLPS from other myxoid or adipose tissue tumors. Moreover, these probe sets are capable of revealing cryptic or variant translocations. Lastly, these data also suggest that EWSR1-DDIT3 is more frequent in pediatric than adult MLPS.
Category: Bone & Soft Tissue

Monday, March 9, 2009 8:45 AM

Platform Session: Section E, Monday Morning