Novel BCOR-MAML3 and ZC3H7B-BCOR gene fusions in undifferentiated small blue round cell sarcomas Journal Article
| Authors: | Specht, K.; Zhang, L.; Sung, Y. S.; Nucci, M.; Dry, S.; Vaiyapuri, S.; Richter, G. H. S.; Fletcher, C. D. M.; Antonescu, C. R. |
| Article Title: | Novel BCOR-MAML3 and ZC3H7B-BCOR gene fusions in undifferentiated small blue round cell sarcomas |
| Abstract: | Small blue round cell tumors (SBRCTs) are a heterogenous group of tumors that are difficult to diagnose because of overlapping morphologic, immunohistochemical, and clinical features. About two-thirds of EWSR1-negative SBRCTs are associated with CIC-DUX4-related fusions, whereas another small subset shows BCOR-CCNB3 X-chromosomal paracentric inversion. Applying paired-end RNA sequencing to an SBRCT index case of a 44-year-old man, we identified a novel BCOR-MAML3 chimeric fusion, which was validated by reverse transcription polymerase chain reaction and fluorescence in situ hybridization techniques. We then screened a total of 75 SBRCTs lacking EWSR1, FUS, SYT, CIC, and BCOR-CCNB3 abnormalities for BCOR break-apart probes by fluorescence in situ hybridization to detect potential recurrent BCOR gene rearrangements outside the typical X-chromosomal inversion. Indeed, 8/75 (11%) SBRCTs showed distinct BCOR gene rearrangements, with 2 cases each showing either a BCOR-MAML3 or the alternative ZC3H7B-BCOR fusion, whereas no fusion partner was detected in the remaining 4 cases. Gene expression of the BCOR-MAML3-positive index case showed a distinct transcriptional profile with upregulation of HOX-gene signature, compared with classic Ewing's sarcoma or CIC-DUX4-positive SBRCTs. The clinicopathologic features of the SBRCTs with alternative BCOR rearrangements were also compared with a group of BCOR-CCNB3 inversion-positive cases, combining 11 from our files with a meta-analysis of 42 published cases. The BCOR-CCNB3-positive tumors occurred preferentially in children and in bone, in contrast to alternative BCOR-rearranged SBRCTs, which presented in young adults, with a variable anatomic distribution. Furthermore, BCOR-rearranged tumors often displayed spindle cell areas, either well defined in intersecting fascicles or blending with the round cell component, which appears distinct from most other fusion-positive SBRCTs and shares histologic overlap with poorly differentiated synovial sarcoma. |
| Keywords: | differentiation; mutations; corepressor; expression; translocation; ewing's sarcoma; transcript; small blue round cell tumor; modular framework; bcor; bcor-maml3; zc3h7b-bcor; ewing-like sarcomas; sinonasal sarcoma |
| Journal Title: | American Journal of Surgical Pathology |
| Volume: | 40 |
| Issue: | 4 |
| ISSN: | 0147-5185 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2016-04-01 |
| Start Page: | 433 |
| End Page: | 442 |
| Language: | English |
| ACCESSION: | WOS:000374901700003 |
| PROVIDER: | wos |
| PMCID: | PMC4792719 |
| PUBMED: | 26752546 |
| DOI: | 10.1097/PAS.0000000000000591 |
| Notes: | Article -- Source: Wos |
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