Abstract 3266
Background
Internal tandem duplications of BCOR (ITD) have been previously observed in pediatric cancers including clear cell sarcoma of the kidney, and rare adult tumors, most recently, in four cases of endometrial stromal sarcoma (ESS) identified by Sanger sequencing (Chiang, 2017; Mariño-Enriquez, 2018). We reviewed the genomic profiles of a large series of advanced cancer patients to identify all cases and diseases harboring BCOR-ITD.
Methods
Tissues from on 140,411 unique advanced cancers were sequenced by hybrid-capture-NGS based comprehensive genomic profiling of 186 to 315 genes plus introns from 14 to 28 genes commonly rearranged in cancer, as well as RNA for 265 genes for a portion of these cases.
Results
BCOR-ITDs were present in 0.024% of all cases (33/140,411), most frequently in sarcomas 63.6% (21/33) either of uterine origin 52.4% (11/21) or in children (non-uterine) 42.8% (9/21). Of the uterine cases, mean age was 42.2 years (range 14-59 years) and referring diagnoses: ESS (6/11), uterine sarcoma (NOS) (2/11), uterine leiomysarcoma (2/11), and undifferentiated uterine sarcoma (1/11). Expert gynecologic pathology central review identified all these cases as having a similar high-grade morphology consistent with ESS, and 90% of cases having a round cell component. The average age of the pediatric sarcoma patients was 3.33 years (range 1-11 years), and most commonly diagnosed as soft tissue sarcoma (NOS) (4/9) and fibrosarcoma (2/9). Cases carrying a BCOR-ITD had a mean Tumor Mutation Burden of 4.12 mut/MB (range 0.8-25.45). The identified BCOR-ITDs occurred most frequently in exon 15, 69.7% (23/33). These exon 15 events had a mean insertion length of 31.7 codons (range 30-38 codons). Of the uterine sarcoma cases harboring exon 15 BCOR-ITDs none simultaneously carried gene fusions typically associated with ESS.
Conclusions
BCOR-ITDs define a rare subset of pediatric and clinically aggressive endometrial stromal sarcoma cases, as defined by NGS for the first time. Our findings along with previous work delineate the pan-cancer landscape of this alteration and suggest the need for focused investigation to delineate the pro-oncogenic function of BCOR, along with any sensitivity to targeted therapies.
Clinical trial identification
Legal entity responsible for the study
Foundation Medicine, Inc.
Funding
Foundation Medicine, Inc.
Editorial Acknowledgement
Disclosure
L. Juckett, R. Madison, C. Patriquin, G.M. Frampton, V.A. Miller, J.S. Ross, J. Chung, A.B. Schrock, S.M. Ali, J.A. Elvin: Employee: Foundation Medicine, Inc.; Equity interest: Foundation Medicine, Inc. All other authors have declared no conflicts of interest.