Abstract 98P
Background
The rare pediatric sarcoma with BCOR and CIC gene rearrangement show biological and clinical distinctions from other URCS. In this retrospective study we compare clinical features sarcoma with BCOR genetic alteration and CIC-rearranged sarcoma in children while assessing the utility of advanced diagnostic algorithms.
Methods
We analyzed of 42 URCS using reverse transcription PCR assay, RNA sequencing and Nanostring technology.
Results
Sarcoma with BCOR genetic alteration was diagnosed in 23 cases, including 17 cases of BCOR::CCNB3 (ex15::ex5), 2 cases of BCOR ITD (ex15), one cases of BCOR::MAML3 (ex15::ex2) and YWHAE::NUTM2B (ex5::ex2); in 2 cases based on gene expression profiles. Median age was 10.5 years (0.25-16.4), the f:m ratio was 1:10. Localized disease observed in 17 cases (74%), 6 cases (26%) had distant metastases. The primary lesion was localized intraosseously in 15 cases (65%), axial skeleton mostly (10 cases), and 8 in soft tissues (35%). 3-year OS and EFS were respectively 96.0±0.04% and 66.8±0.12% (p=0.01). There were no statistically significance differences in distribution of EFS depends on treatment protocols (EuroEwing or CWS) in patients with sarcoma with BCOR genetic alteration (p = 0.571). CIC-rearranged sarcoma was diagnosed in 14 cases: 5 cases of CIC::DUX4 (mostly ex21::ex1), 4 cases of CIC ex21, 2 cases of CIC::DUX4L9 (ex16::ex1 and ex21::ex1), 1 case of CIC::NUTM2B (ex20::intr4), in 2 cases was verified regards gene expression profiles. The median age at diagnosis was 14.4 years (1.76-16.6), the f:m ratio was 4:10. Distant metastasis observed in 8 cases (57%), 6 cases (43%) had localized decease. The primary lesion was localized in soft tissues (12 cases, 86%) or intraosseously (2 cases, 14%). 3-year OS and RFS in this group were respectively 34.4±16.0% and 23.8±14.6 (p=0.014).
Conclusions
NanoString technology demonstrate advantage in the extremely high levels of RNA degradation samples and difficult-to-detect CIC fusion transcripts. Sarcoma with BCOR genetic alteration demonstrates predominance in males, axial skeleton bones affinity, high rate of late relapse. CIC-rearranged sarcoma associated with an aggressive clinical course, high frequent of the distant metastases and fatal relapses.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
“Science for Children” foundation.
Disclosure
All authors have declared no conflicts of interest.