Frequent mutations in the amino-terminal domain of BCL7A impair its tumor suppressor role in DLBCL
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ABSTRACT:
PROVIDER: PRJNA627880 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11604776_1.fastq.gz | Fastqsanger.gz | |||
| SRR11604776_2.fastq.gz | Fastqsanger.gz | |||
| SRR11604777_1.fastq.gz | Fastqsanger.gz | |||
| SRR11604777_2.fastq.gz | Fastqsanger.gz | |||
| SRR11604778_1.fastq.gz | Fastqsanger.gz |
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Project description:Mutations in genes encoding the various subunits of the SWI/SNF chromatin remodeling complex are frequently observed in different human cancers. In diffuse large B-cell lymphoma (DLBCL), genetic changes in BCL7A, a subunit of the SWI/SNF complex, have been recently reported but the functional role of such genetic changes remains unknown. BCL7A mutations concentrate at the first exon and the most frequently mutated hotspot is the splice donor site of the first intron. By using in vitro and in vivo analyses, we show that restoration of BCL7A drives a tumor suppressor-like phenotype. Further, we found that splice site mutations block the tumor suppressor phenotype and prevent BCL7A from binding to the SWI/SNF complex. Finally, we identified that the SWI/SNF complex accumulates mutations in a third of DLBCL tumors, especially in the GCB subtype. These discoveries highlight the tumor suppressor role of BCL7A mutations in DLBCL, and suggest that the SWI/SNF complex is involved in DLBCL pathogenesis.
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Project description:Mutations in genes encoding the various subunits of the SWI/SNF chromatin remodeling complex are frequently observed in different human cancers. In diffuse large B-cell lymphoma (DLBCL), genetic changes in BCL7A, a subunit of the SWI/SNF complex, have been recently reported but the functional role of such genetic changes remains unknown. BCL7A mutations concentrate at the first exon and the most frequently mutated hotspot is the splice donor site of the first intron. By using in vitro and in vivo analyses, we show that restoration of BCL7A drives a tumor suppressor-like phenotype. Further, we found that splice site mutations block the tumor suppressor phenotype and prevent BCL7A from binding to the SWI/SNF complex. Finally, we identified that the SWI/SNF complex accumulates mutations in a third of DLBCL tumors, especially in the GCB subtype. These discoveries highlight the tumor suppressor role of BCL7A mutations in DLBCL, and suggest that the SWI/SNF complex is involved in DLBCL pathogenesis.
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