[29] Recurrent t(4;19) Translocation with CIC-DUX4 Fusion in a Novel Highly Malignant Small Round Cell Soft Tissue Sarcoma

Eun-Young K Choi, Dafydd G Thomas, Jonathan B McHugh, Rajiv M Patel, Diane Roulston, Christopher Wienczewski, Mitual B Amin, David R Lucas. University of Michigan, Ann Arbor, MI; William Beaumont Hospital, Royal Oak, MI

Background: Translocation-associated sarcomas are defined by distinctive histologic patterns and clinical behavior. Only 8 cases of small round cell soft tissue sarcomas (SRCSTS) harboring t(4;19)(q35;q13.1) have previously been reported, mostly in the pediatric population. In these tumors, CIC on chr 19 fuses with DUX4 on chr 4 resulting in a putative oncogene, CIC-DUX4. Herein we describe 4 new cases of SRCSTS harboring this novel recurrent translocation in young adult patients.
Design: We identified 2 initial cases of SRCSTS with complex karyotypes that had t(4;19)(q35;q13.1) translocations. To confirm CIC-DUX4 fusion and to identify additional cases with t(4;19), we designed RT-PCR primers to detect CIC-DUX4 fusion and FISH probes to detect CIC-DUX4 fusion as well as chr 19q13 break-apart. Paraffin blocks from 19 additional cases with similar histologic findings to our initial 2 cases were selected for CIC-DUX4 testing.
Results: RT-PCR and FISH assays for CIC-DUX4 fusion and chr 19q13 break-apart confirmed CIC-DUX4 fusion in our initial 2 cases, which were also negative for Ewings and synovial sarcoma translocations by cytogenetics, RT-PCR and FISH. Of the 19 additional cases, 2 were positive for the CIC-DUX4 fusion by FISH and negative for EWS-FLI1 by RT-PCR. The cohort consisted of 2 women (ages 25 & 32) and 2 men (ages 20 & 31). Each presented with a rapidly growing soft tissue mass (mean tumor size 12.8 cm). 2 were located in the thigh, and 1 each in the perineum and calf. All 4 tumors had similar histological features consisting of sheets of primitive small round blue cells with scant cytoplasm, slightly myxoid background, and large zones of necrosis. Only 1 tumor expressed CD99. All 4 patients received neoadjuvant and adjuvant chemotherapy and surgical resection of the primary tumor. 2 had lung metastasis at presentation and a third developed lung and spine metastases 6 months after presentation; all 3 were unresponsive to therapy and died of disease (mean survival 10.6 months). The fourth patient responded to therapy and is alive without evidence of recurrence or metastasis at 27 months.
Conclusions: CIC-DUX4 primitive SRCSTS represents a novel translocation-associated sarcoma. Our preliminary results suggest aggressive clinical behavior and failure to respond to conventional treatment. Additional FISH and RT-PCR assays are currently being performed for further confirmation and to identify more cases. The results will be reported at the meeting.
Category: Bone & Soft Tissue

Tuesday, March 20, 2012 8:15 AM

Platform Session: Section G, Tuesday Morning


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