Chromatin remodeling (SWI/SNF) complexes, cancer, and response to immunotherapy
Chromatin regulation involves four subfamilies composed of ATP-dependent multifunctional protein complexes that remodel the way DNA is packaged. The SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex subfamily mediates nucleosome reorganization and hence activation/repression of c...
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| Language: | English |
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BMJ Publishing Group
2022-09-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/10/9/e004669.full |
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| author | Razelle Kurzrock Shumei Kato Nithya Krishnamurthy Scott Lippman |
| author_facet | Razelle Kurzrock Shumei Kato Nithya Krishnamurthy Scott Lippman |
| author_sort | Razelle Kurzrock |
| collection | DOAJ |
| description | Chromatin regulation involves four subfamilies composed of ATP-dependent multifunctional protein complexes that remodel the way DNA is packaged. The SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex subfamily mediates nucleosome reorganization and hence activation/repression of critical genes. The SWI/SNF complex is composed of the BRG-/BRM-associated factor and Polybromo-associated BAF complexes, which in turn have multiple subunits. Significantly, ~20% of malignancies harbor alterations in >1 of these subunits, making the genes encoding SWI/SNF family members among the most vulnerable to genomic aberrations in cancer. ARID1A is the largest subunit of the SWI/SNF complex and is altered in ~40%–50% of ovarian clear cell cancers and ~15%–30% of cholangiocarcinomas, in addition to a variety of other malignancies. Importantly, outcome was improved after immune checkpoint blockade (ICB) in patients with ARID1A-altered versuss wild-type tumors, and this result was independent of microsatellite instability or tumor mutational burden. Another subunit—PBRM1—is mutated in ~40% of clear cell renal cell carcinomas and ~12% of cholangiocarcinomas; there are contradictory reports regarding ICB responsiveness. Two other SWI/SNF subunits of interest are SMARCA4 and SMARCB1. SMARCA4 loss is the hallmark of small cell carcinoma of the ovary hypercalcemic type (and is found in a variety of other malignancies); SMARCA4 germline alterations lead to rhabdoid tumor predisposition syndrome-2; SMARCB1 germline alterations, rhabdoid tumor predisposition syndrome-1. Remarkable, although anecdotal, responses to ICB have been reported in both SMARCA4-aberrant and SMARCB1-aberrant advanced cancers. This review focuses on the role that SWI/SNF chromatin remodeling subunits play in carcinogenesis, the immune microenvironment, and in immunotherapy responsiveness. |
| format | Article |
| id | doaj-art-174b464f7edf44f2922e8ce406e2045c |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2022-09-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-174b464f7edf44f2922e8ce406e2045c2025-02-09T09:25:15ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262022-09-0110910.1136/jitc-2022-004669Chromatin remodeling (SWI/SNF) complexes, cancer, and response to immunotherapyRazelle Kurzrock0Shumei Kato1Nithya Krishnamurthy2Scott Lippman35MCW Cancer Center and Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, WI, USA1Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, University of California San Diego, Moores Cancer Center, La Jolla, CA, USAIcahn School of Medicine at Mount Sinai, New York, New York, USAIcahn School of Medicine at Mount Sinai, New York, New York, USAChromatin regulation involves four subfamilies composed of ATP-dependent multifunctional protein complexes that remodel the way DNA is packaged. The SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex subfamily mediates nucleosome reorganization and hence activation/repression of critical genes. The SWI/SNF complex is composed of the BRG-/BRM-associated factor and Polybromo-associated BAF complexes, which in turn have multiple subunits. Significantly, ~20% of malignancies harbor alterations in >1 of these subunits, making the genes encoding SWI/SNF family members among the most vulnerable to genomic aberrations in cancer. ARID1A is the largest subunit of the SWI/SNF complex and is altered in ~40%–50% of ovarian clear cell cancers and ~15%–30% of cholangiocarcinomas, in addition to a variety of other malignancies. Importantly, outcome was improved after immune checkpoint blockade (ICB) in patients with ARID1A-altered versuss wild-type tumors, and this result was independent of microsatellite instability or tumor mutational burden. Another subunit—PBRM1—is mutated in ~40% of clear cell renal cell carcinomas and ~12% of cholangiocarcinomas; there are contradictory reports regarding ICB responsiveness. Two other SWI/SNF subunits of interest are SMARCA4 and SMARCB1. SMARCA4 loss is the hallmark of small cell carcinoma of the ovary hypercalcemic type (and is found in a variety of other malignancies); SMARCA4 germline alterations lead to rhabdoid tumor predisposition syndrome-2; SMARCB1 germline alterations, rhabdoid tumor predisposition syndrome-1. Remarkable, although anecdotal, responses to ICB have been reported in both SMARCA4-aberrant and SMARCB1-aberrant advanced cancers. This review focuses on the role that SWI/SNF chromatin remodeling subunits play in carcinogenesis, the immune microenvironment, and in immunotherapy responsiveness.https://jitc.bmj.com/content/10/9/e004669.full |
| spellingShingle | Razelle Kurzrock Shumei Kato Nithya Krishnamurthy Scott Lippman Chromatin remodeling (SWI/SNF) complexes, cancer, and response to immunotherapy Journal for ImmunoTherapy of Cancer |
| title | Chromatin remodeling (SWI/SNF) complexes, cancer, and response to immunotherapy |
| title_full | Chromatin remodeling (SWI/SNF) complexes, cancer, and response to immunotherapy |
| title_fullStr | Chromatin remodeling (SWI/SNF) complexes, cancer, and response to immunotherapy |
| title_full_unstemmed | Chromatin remodeling (SWI/SNF) complexes, cancer, and response to immunotherapy |
| title_short | Chromatin remodeling (SWI/SNF) complexes, cancer, and response to immunotherapy |
| title_sort | chromatin remodeling swi snf complexes cancer and response to immunotherapy |
| url | https://jitc.bmj.com/content/10/9/e004669.full |
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