Soft Tissue and Visceral Organ Sarcomas With BCOR Alterations

Abstract

Sarcomas with BCOR alteration are a heterogenous group characterized by changes including internal tandem duplications (ITDs) and recurring fusions with CCNB3, ZC3H7B, and other rare partners. With widespread genomic testing, these alterations are now associated with histologies such as Ewing-like sarcoma (BCOR:: CCNB3), high-grade endometrial stromal sarcoma (ZC3H7B:: BCOR), and clear cell sarcoma of kidney (BCOR-ITD). BCOR altered sarcomas of soft tissues and organs were identified through PubMed using keywords "Sarcoma (AND) BCOR" from 2005 through October 2021. Summary statistics and outcome data were calculated using STATA v12.1. Forty-one publications described 190 patients with BCOR altered soft tissue or organ sarcomas. BCOR-ITD was most common, followed by BCOR::CCNB3, ZC3H7B:: BCOR. BCOR-ITD tumors occurred mainly in infants, BCOR:: CCNB3 commonly occurred in adolescent young adults, and ZC3H7B::BCOR only in adults. The most common site for BCOR:: CCNB3 fused tumors was extremity, BCOR-ITD kidney and ZC3H7B::BCOR uterus. Metastasis was rare in patients with BCOR::CCNB3. While most underwent resection and chemotherapy, few received radiation. Median follow-up of survivors was 24 months. Five year overall survival for patients with BCOR::CCNB3 fusions was 68% (95% confidence interval [CI]: 46%-83%). Patients with BCOR-ITD and ZC3H7B::BCOR had worse prognoses with 5 years overall survival of 35% (95% CI: 15%-56%) and 41% (95% CI: 11%-71%), respectively, demonstrating need for collaborative efforts identifying optimal treatments to improve outcomes.

Clinical characteristics and outcomes for children, adolescents and young adults with “CIC‐fused” or “BCOR‐rearranged” soft tissue sarcomas: A multi‐institutional European retrospective analysis

“…29 In contrast, "BCOR rearranged sarcomas" are described as occurring more frequently in bone (64%) and in pediatric patients (76%) 30 : BCOR::CCNB was described more often in adolescents in contrast to BCOR-ITD, more frequently occurring in infants. [30][31][32] In our study, we cannot demonstrate any difference in the age of occurrence comparing BCOR::CCNB to other genetic alterations as BCOR-ITD or the YWHAE alteration in contrast to data referring to all locations. 31 Our cohort of patients harboring the BCOR rearrangement frequently had localized tumor, located in limbs and significantly younger at diagnosis than patients with "CIC fused" STS, confirming observations including locations in bone.…”

“…[30][31][32] In our study, we cannot demonstrate any difference in the age of occurrence comparing BCOR::CCNB to other genetic alterations as BCOR-ITD or the YWHAE alteration in contrast to data referring to all locations. 31 Our cohort of patients harboring the BCOR rearrangement frequently had localized tumor, located in limbs and significantly younger at diagnosis than patients with "CIC fused" STS, confirming observations including locations in bone. 30 Interestingly, we confirm that age was a significant factor for EFS, especially for BCOR/YWHA tumors, but not the biological entity itself.…”

“…These different genetic alterations seem to have a prognostic impact as patients with BCOR altered tumors are reported to have an overall poor prognosis. BCOR::CCNB3 fused tumors are reported to have a 5‐year OS of 68%, in contrast to patients with BCOR‐ITD or ZC3H7B::BCOR tumors that have low survival rates, with more than 50% of patients in each group dying of relapse of their disease 31 . In our experience we report a much higher number of IRS group IV tumors in the “ CIC fused sarcomas” and only two in the “ BCOR rearranged sarcomas” at diagnosis.…”

A novel case of malignant ossifying fibromyxoid tumor with a BCOR internal tandem duplication in a child

“…20 Several different BCOR alterations have been found in various soft tissue and visceral organ sarcomas in children and adults. 21 One such alteration, BCOR internal tandem duplication (BCOR-ITD), was first identified as an oncogenic driver in clear cell sarcoma of kidney (CCSK) and has not been previously reported with OFMT. 22 Herein, we present a novel case of a 16-year-old female with an original diagnosis of localized atypical OFMT whose tumor was found to have malignant features and a BCOR-ITD upon second (local and metastatic) recurrence.…”

“…31 Among such tumors, the BCOR-ITD alteration most frequently occurs in infants with CCSK. 21,32 Nearly all BCOR-ITDs result from somatic in-frame tandem duplications of greater than or equal to three base pairs in exon 15 of BCOR. BCOR-ITDs are detected primarily using fragment length analysis or NGS.…”