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Oncology. 2019;96(2):101-109. doi: 10.1159/000493322. Epub 2018 Oct 31.

A Pan-Cancer Landscape Analysis Reveals a Subset of Endometrial Stromal and Pediatric Tumors Defined by Internal Tandem Duplications of BCOR.

Author information

Foundation Medicine Inc., Cambridge, Massachusetts,
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Foundation Medicine Inc., Cambridge, Massachusetts, USA.



The Polycomb Repressive Complex 1 (PRC1) regulates epigenetic silencing and is manifestly linked to rare cancer types. The X-linked BCOR gene (BCL-6 Corepressor) is a member of the PRC1 complex and potentiates transcriptional repression through BCL6 binding of PRC1. Accumulating evidence suggests that internal tandem duplications (ITD) of BCOR are oncogenic drivers in a subset of pediatric sarcomas and rare adult tumors.


We reviewed the genomic profiles of a large series of advanced cancer patients to determine the frequency and genomic spectrum of ITD of BCOR across cancer.


Tissues from 140,411 unique advanced cancers were sequenced by hybrid-capture-NGS-based comprehensive genomic profiling of 186-315 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.


BCOR-ITDs were present in 0.024% of all cases (33/140,411). Of this dataset, sarcoma cancer types were most frequent, 63.6% (21/33), either of uterine origin 52.4% (11/21), or pediatric (nonuterine) 42.8% (9/21). The identified BCOR-ITDs occurred most frequently in exon 15, near C-terminus, 69.7% (23/33), with a mean insertion length of 31.7 codons (range 30-38). Of uterine cases, an expert gynecologic pathology central review identified all these cases as having a similar high-grade morphology consistent with endometrial stromal sarcomas (ESS), and 90% of cases having a round cell component. Of the uterine sarcoma cases harboring exon 15 BCOR-ITDs, none simultaneously carried gene fusions typically associated with ESS.


BCOR-ITDs define a rare subset of pediatric sarcomas and clinically aggressive endometrial stromal sarcoma cases, as defined by NGS for the first time. Our findings help 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.


BCOR gene; Duplication; Endometrial stromal sarcomas; Internal tandem duplications

[Indexed for MEDLINE]

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