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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

1
Foundation Medicine Inc., Cambridge, Massachusetts, USAljuckett@foundationmedicine.com.
2
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
3
Foundation Medicine Inc., Cambridge, Massachusetts, USA.

Abstract

BACKGROUND:

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.

OBJECTIVE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

KEYWORDS:

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

PMID:
30380541
DOI:
10.1159/000493322
[Indexed for MEDLINE]

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