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Updated: Jan 24, 2026
Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma
Published on: April 11, 2018
Loss of Expression of a Novel Chromatin Remodeler SMARCA1 in Soft Tissue Sarcoma
Pallavi A Patil1, Kara Lombardo1, Ashlee Sturtevant1
1Department of Pathology, Warren Alpert Medical School of Brown University, Lifespan Academic Medical Center, Providence, Rhode Island, USA.
Introduction:
Vital cellular processes such as proliferation and differentiation are regulated by chromatin remodeling complexes. A variety of neoplasms have been discovered to have genomic alterations (GAs) and loss of immunohistochemical (IHC) expression of chromatin remodelers ARID1A (BAF250A), SMARCA2 (BRM), SMARCA4 (BRG1), and SMARCB1 (INI1). SMARCA1 (SNF2L) is another member of the chromatin remodelers, and has not yet been studied in neoplasia. As SMARCA1 is located on chromosome X, could be potentially inactivated by a single hit. We aimed to evaluate GAs and protein expression of SMARCA1 in soft tissue tumors.
Method:
The publically available cBioPortal.32e34 platform was queried to analyze data on soft tissue tumors from The Cancer Genome Atlas project (TCGA) related to SMARCA1 GAs. Our institutional archives were queried to collect 26 cases of soft tissue tumors including 10 undifferentiated sarcomas, 5 leiomyosarcomas, 6 liposarcomas, and 5 malignant peripheral sheath tumors (MPNST). IHC for SMARCA1 with an SNF 2C4 monoclonal antibody was performed on whole tissue sections.
Results:
SMARCA1 GAs were present in 8/261 soft tissue sarcomas (3%) in the TCGA dataset. Leiomyosarcomas had most common SMARCA1 GAs in 6/99 cases. SMARCA1 deletions existed in 1/56 dedifferentiated liposarcomas and 1/48 undifferentiated sarcomas. No SMARCA1 GAs occurred in other sarcoma subtypes. SMARCA1 IHC was studied in the sarcoma subtypes with potential SMARCA1 alterations in our institutional cases. SMARCA1 nuclear expression was lost in 3/10 cases (30%) of undifferentiated sarcoma, and 2/5 cases of MPNST (40%). SMARCA1 expression was intact in all cases of leiomyosarcoma and liposarcoma.
Conclusion:
This is the first study to demonstrate loss of expression of SMARCA1 in soft tissue sarcomas subtypes, including undifferentiated sarcoma. Our study highlights merit for further investigation on the role of SMARCA1 in the differentiation process and molecular mechanisms of SMARCA1 inactivation.
Insights
This study investigated genomic alterations and protein expression of SMARCA1 in soft tissue tumors. SMARCA1 (SNF2L) loss was observed in undifferentiated sarcoma and malignant peripheral nerve sheath tumors, suggesting a role in tumorigenesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chromatin remodeling complexes regulate vital cellular processes like proliferation and differentiation.
- Genomic alterations and loss of expression of several chromatin remodelers are observed in various neoplasms.
- SMARCA1 (SNF2L), a chromatin remodeler on the X chromosome, has not been studied in neoplasia.
Purpose of the Study:
- To evaluate genomic alterations (GAs) and protein expression of SMARCA1 in soft tissue tumors.
- To investigate the potential role of SMARCA1 inactivation in soft tissue tumor development.
Main Methods:
- Analysis of SMARCA1 GAs in soft tissue tumors using The Cancer Genome Atlas (TCGA) data via cBioPortal.
- Immunohistochemistry (IHC) for SMARCA1 protein expression on 26 institutional soft tissue tumor cases, including undifferentiated sarcomas, leiomyosarcomas, liposarcomas, and malignant peripheral nerve sheath tumors (MPNST).
Main Results:
- SMARCA1 GAs were found in 3% of soft tissue sarcomas in the TCGA dataset, most commonly in leiomyosarcomas (6/99).
- SMARCA1 nuclear expression was lost in 30% of undifferentiated sarcomas and 40% of MPNST cases.
- SMARCA1 expression remained intact in all studied leiomyosarcomas and liposarcomas.
Conclusions:
- This is the first study to report loss of SMARCA1 expression in soft tissue sarcoma subtypes, notably undifferentiated sarcoma.
- Further investigation into the role of SMARCA1 in cellular differentiation and its molecular inactivation mechanisms is warranted.
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