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Results for “SMARCB1”

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5 recordsLinked to original sources

PubMed2026

Myoepithelioma-like tumor of the vulvar region shows a quiet genome and heterogeneous detectable mechanisms of SMARCB1 inactivation: Integrated analysis of two cases and review of the literature.

Myoepithelioma-like tumor of the vulvar region (MELTVR) is a rare SMARCB1-deficient mesenchymal neoplasm of adult women that can mimic malignant vulvar sarcomas, particularly epithelioid sarcoma. Although loss of SMARCB1/INI1 expression is a defining feature, the comprehensive genomic landscape of MELTVR remains poorly characterized. We report two cases of MELTVR and performed integrated histopathologic, immunophenotypic, and molecular analyses, including whole-exome sequencing (WES) with copy number assessment and targeted RNA-based fusion testing using the Archer FusionPlex Sarcoma panel. Histologically, both tumors consisted of relatively uniform epithelioid to short spindle cells in solid nests and cords within focal myxoid stroma, with complete loss of INI1 and positivity for smooth muscle markers and focal ER/EMA expression. Genomic profiling demonstrated a quiet molecular background in both cases, with low tumor mutation burden (0.45 and 1.03 mut/Mb) and no pathogenic SNVs/indels in major cancer-associated genes. One case showed a focal homozygous deletion of the SMARCB1 locus at 22q11.2, whereas the other case exhibited INI1 loss without detectable SMARCB1 mutation or copy number loss, suggesting heterogeneous mechanisms of inactivation. CDKN2A copy number remained neutral in both tumors. No canonical sarcoma-associated gene rearrangements, including EWSR1, FUS, PLAG1, or NR4A3, were identified. Together with a review of previously reported cases, these findings support MELTVR as an SMARCB1-inactivated neoplasm with low genomic complexity and highlight the diagnostic value of NGS-based profiling in excluding malignant mimics and preventing overtreatment.

Humans↗

PubMed2026

Two cases of mosaic germline SVA insertions in SMARCB1: implications for rhabdoid tumour predisposition diagnosis.

Rhabdoid tumour predisposition syndrome (RTPS) is a highly penetrant cancer predisposition syndrome caused by germline variants in SMARCB1 or less frequently in SMARCA4. Genetic testing for this syndrome involves sequence and deletion/duplication analysis of these two genes. Standard clinical testing is limited in detecting structural variants. Here we describe two patients who tested negative on standard clinical germline panel testing for RTPS but were each found to have a mosaic germline insertion of an SVA (SINE-VNTR-Alu) element in the SMARCB1 gene by more advanced comprehensive genomic analysis. These two cases demonstrate the importance of structural variants and broader genomic sequencing for individuals suspected of having an underlying germline cancer predisposition syndrome, such as RTPS.

Journal Article↗

PubMed2026

Identification of the Genomic Etiology of Unexplained Congenital Problems in Pediatric Patients: First Reported Case With Coffin-Siris Syndrome and Sialuria From India.

Coffin-Siris syndrome (CSS) (OMIM:614608) is a rare genetic disorder characterized by global developmental delay (GDD), speech impediment, coarse facial features, and hypoplastic or absent fifth fingernails/toenails. Genetic variants in the SMARCB1 gene are associated with CSS, benign tumors (schwannomas), and rhabdoid tumor predisposition syndrome. Genetic variants in the GNE gene are associated with the autosomal dominant sialuria (OMIM#269921), a rare inborn error of metabolism resulting in high levels of free sialic acid. Here we present case reports of two siblings: patient 1 (10 years) and patient 2 (2 years). While both siblings showed GDD and dysmorphic features such as hypotelorism and large ears, patient #1 exhibited additional phenotypes. Whole exome sequencing identified a heterozygous pathogenic variant, NM_003073.5:c.1096C>T (p.Arg366Cys), in the SMARCB1 gene in both siblings. In addition, patient 1 harbored a heterozygous likely pathogenic variant, NM_005476.7:c.2086G>A (p.Val696Met), in the GNE gene, which was absent in patient 2. The co-occurrence of the GNE variant may contribute to the increased severity of the phenotype in patient 1. This study is the first report worldwide of the co-occurrence of two extremely rare disorders. These findings highlight the complexity of genomic contributions while also emphasizing the value of genomic sequencing for congenital problems.

Coffin–Siris syndrome↗

PubMed1992

Evidence that SNF2/SWI2 and SNF5 activate transcription in yeast by altering chromatin structure.

Changes in chromatin structure have frequently been correlated with changes in transcription. However, the cause-and-effect relationship between chromatin structure and transcription has been hard to determine. In addition, identifying the proteins that regulate chromatin structure has been difficult. Recent evidence suggests that a functionally related set of yeast transcriptional activators (SNF2/SWI2, SNF5, SNF6, SWI1, and SWI3), required for transcription of a diverse set of genes, may affect chromatin structure. We now present genetic and molecular evidence that at least two of these transcriptional activators, SNF2/SWI2 and SNF5, function by antagonizing repression mediated by nucleosomes. First, the transcriptional defects in strains lacking these SNF genes are suppressed by a deletion of one of the two sets of genes encoding histones H2A and H2B, (hta1-htb1) delta. Second, at one affected promoter (SUC2), chromatin structure is altered in snf2/swi2 and snf5 mutants, and this chromatin defect is suppressed by (hta1-htb1) delta. Finally, analysis of chromatin structure at a mutant SUC2 promoter, in which the TATA box has been destroyed, demonstrates that the differences in SUC2 chromatin structure between SNF5+ and snf5 mutant strains are not simply an effect of different levels of SUC2 transcription. Thus, these results strongly suggest that SNF2/SWI2 and SNF5 cause changes in chromatin structure and that these changes allow transcriptional activation.

Adenosine Triphosphatases↗

PubMed1992

Yeast SNF2/SWI2, SNF5, and SNF6 proteins function coordinately with the gene-specific transcriptional activators GAL4 and Bicoid.

The SNF2 (SWI2), SNF5, and SNF6 genes are required for transcription of many diversely regulated genes in Saccharomyces cerevisiae. Previously, we showed that SNF2, SNF5, and SNF6 function interdependently in transcriptional activation, possibly forming a heteromeric complex. Here, we present evidence that SNF6 has a more direct role in stimulating transcription than SNF2 and SNF5. The global effects of mutations in SNF2, SNF5, and SNF6 suggested that these SNF proteins may function coordinately with many gene-specific activators. We show that LexA-GAL4 and LexA-Bicoid fusion proteins are both dependent on SNF2, SNF5, and SNF6 for activation of target genes containing one or multiple lexA operators. The stringency of the requirement for the SNF proteins varies with the activator, the number of binding sites for the activator, and the target promoter. Thus, these SNF proteins appear to represent a class of intermediary proteins that facilitate transcriptional activation by gene-specific regulatory proteins.

Adenosine Triphosphatases↗