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SS18-SSX-mediated hijacking of BAF complexes drives synovial sarcoma

Synovial sarcoma (SS) is defined by a recurrent t(x;18) chromosomal translocation, which produces the hallmark SS18-SSX oncogenic fusion. Incorporation of SS18-SSX into BAF complexes renders BAF complexes aberrant in two distinct manners: the addition of 78aa of SSX onto SS18, and concomitant loss of BAF47 assembly. However, the importance and functional contributions of each of these perturbations on BAF complex targeting and gene expression regulation remain unclear. Here we use an integrative set of genomic approaches in human cancer cell lines and primary tumor samples to define the mechanistic consequences of the SS18-SSX fusion oncoprotein. We find that SS18-SSX hijacks BAF complexes to broad polycomb domains to activate bivalent genes, driving a unique gene expression program distinct from other loss-of-function BAF complex malignancies. Importantly, restoration of BAF47 rescues enhancer activation but is dispensable for proliferative arrest in cell lines. These results demonstrate that gain-of-function SS18-SSX-mediated BAF complex targeting and gene activation is the driving event in SS, and present a mechanism by which distinct functions of BAF complexes can be co-opted to drive oncogenesis.

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UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER DEPARTMENT OF GENOMIC MEDICINE DATA ACCESS AGREEMENT

UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER DEPARTMENT OF GENOMIC MEDICINE DATA ACCESS AGREEMENT This agreement discloses the conditions under which any human genomic, proteomic, and immune profiling Data generated by the University of Texas Department of Genomic Medicine is to be accessed from public databases such as dbGAP and EGA. By signing this agreement, you, the User and Associates (collaborators, staff scientists, and trainees) agree to abide by the terms and conditions of data access set out in this agreement. Terms and Conditions: 1. The Data is to be used for research only including analyses of somatic, germline, structural variants, differential expression patterns, and immune infiltrates. 2. The Data is to be stored in an appropriate password-protected computational infrastructure monitored by your institutional information technology group. 3. You, as the User, are a laboratory head, principal investigator and take responsibility for the distribution, use, storage, and management of the Data in question. 4. You, the User and any collaborators, staff scientists, and trainees are to be co-signees of an IRB-protocol for the use of this data. The IRB protocol number should be referenced in the Materials Transfers Agreement. 5. The Materials Transfers Agreement should also state the purpose and goal of the Data usage. 6. You may use the Data for research that could result in intellectual property or commercial product. 7. Confidentiality of Data Subjects will be preserved by you the User and Associates. 8. The accession number of the study under which the Data is received should be incorporated and referenced appropriately in any publication that results from use of the Data. 9. Any breach of this agreement will result in termination and immediate permanent deletion of Data. 10. The Data is subject to international laws. Database: ___________________________________ Study Accession Number: ___________________________ Name of Applicant(s): ______________________________ _______________________________ _______________________________ Signature of Applicant(s) ___________________________ ______________________________ _________________________________ Email address of Applicant(s): _______________________ ________________________ _________________________ Telephone number of Applicant(s): ___________________ Name of the Information Technology Director of the Institution: _______________________________ Signature of the Institutional Authority: ______________________________ Print Name: __________________________ User Institution:_______________________ Date:_________________________________

Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
Other

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Located in
EGAF00002005591 fastq.gz 3.5 GB
EGAF00002005592 fastq.gz 3.3 GB
EGAF00002005593 fastq.gz 3.0 GB
EGAF00002005594 fastq.gz 3.0 GB
EGAF00002005595 fastq.gz 3.1 GB
EGAF00002005596 fastq.gz 3.8 GB
EGAF00002005597 fastq.gz 1.7 GB
EGAF00002005598 fastq.gz 3.1 GB
EGAF00002005599 fastq.gz 3.1 GB
EGAF00002005600 fastq.gz 1.5 GB
EGAF00002005601 fastq.gz 1.2 GB
EGAF00002005602 fastq.gz 997.0 MB
EGAF00002005603 fastq.gz 1.1 GB
EGAF00002005604 fastq.gz 1.1 GB
EGAF00002005605 fastq.gz 1.1 GB
EGAF00002005606 fastq.gz 1.4 GB
EGAF00002005607 fastq.gz 973.9 MB
EGAF00002005608 fastq.gz 2.1 GB
EGAF00002005609 fastq.gz 1.5 GB
EGAF00002005610 fastq.gz 304.0 MB
EGAF00002005611 fastq.gz 2.1 GB
EGAF00002005612 fastq.gz 2.2 GB
EGAF00002005613 fastq.gz 1.7 GB
EGAF00002005614 fastq.gz 907.0 MB
EGAF00002005615 fastq.gz 2.0 GB
EGAF00002005616 fastq.gz 1.5 GB
EGAF00002005617 fastq.gz 1.4 GB
EGAF00002005618 fastq.gz 1.3 GB
EGAF00002005619 fastq.gz 1.3 GB
EGAF00002005620 fastq.gz 1.6 GB
EGAF00002005621 fastq.gz 1.6 GB
EGAF00002005622 fastq.gz 1.6 GB
EGAF00002005623 fastq.gz 1.1 GB
EGAF00002005624 fastq.gz 1.3 GB
EGAF00002005625 fastq.gz 1.5 GB
EGAF00002005626 fastq.gz 8.7 GB
EGAF00002005627 fastq.gz 3.1 GB
EGAF00002005628 fastq.gz 3.5 GB
EGAF00002005629 fastq.gz 3.8 GB
EGAF00002005630 fastq.gz 3.4 GB
EGAF00002005631 fastq.gz 3.3 GB
EGAF00002005632 fastq.gz 3.3 GB
EGAF00002005633 fastq.gz 1.4 GB
EGAF00002005634 fastq.gz 1.2 GB
EGAF00002005635 fastq.gz 1.4 GB
EGAF00002005636 fastq.gz 1.2 GB
EGAF00002005637 fastq.gz 1.3 GB
EGAF00002005638 fastq.gz 1.3 GB
48 Files (100.8 GB)