ArticleOncogene2011
Two novel BRM insertion promoter sequence variants are associated with loss of BRM expression and lung cancer risk.
Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Genome-wide association study of INDELs identified four novel susceptibility loci associated with lung cancer risk.International journal of cancer · 2020Pooled it
- BRM Promoter Polymorphisms and Survival of Advanced Non-Small Cell Lung Cancer Patients in the Princess Margaret Cohort and CCTG BR.24 Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- Gene regulatory network transitions reveal the central transcription factors in lung adenocarcinoma progression.NPJ systems biology and applications · 2026Article
- The role of SMARCA4 in lung cancer.Scientific reports · 2025Review
- SMARCA4 deficiency in small cell lung cancer: A case report and narrative review of the literature.Biomolecules & biomedicine · 2025Review
- Promoter/enhancer-based controllability of regulatory networks.Scientific reports · 2022Article
- SMARCA2 deficiency in NSCLC: a clinicopathologic and immunohistochemical analysis of a large series from a single institution.Environmental health and preventive medicine · 2022Article
- Identification of potential diagnostic and prognostic biomarkers for LUAD based on TCGA and GEO databases.Bioscience reports · 2021Article
- Article
- BRM: the core ATPase subunit of SWI/SNF chromatin-remodelling complex-a tumour suppressor or tumour-promoting factor?Epigenetics & chromatin · 2019Review
- Remodeling the cancer epigenome: mutations in the SWI/SNF complex offer new therapeutic opportunities.Expert review of anticancer therapy · 2019Review
- Article
- Article
- Incorporating epistasis interaction of genetic susceptibility single nucleotide polymorphisms in a lung cancer risk prediction model.International journal of oncology · 2016Article
- The dark matter of the cancer genome: aberrations in regulatory elements, untranslated regions, splice sites, non-coding RNA and synonymous mutations.EMBO molecular medicine · 2016Review
- Concomitant loss of SMARCA2 and SMARCA4 expression in small cell carcinoma of the ovary, hypercalcemic type.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2016Article
- BRG1 and BRM loss selectively impacts RB and P53, respectively: BRG1 and BRM have differential functionsOncoscience · 2016Article
- The search for cis-regulatory driver mutations in cancer genomes.Oncotarget · 2015Review
- Induction of functional Brm protein from Brm knockout mice.Oncoscience · 2015Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
SWI/SNF (SWItch/sucrose non-fermentable) complexes are ATP-dependent chromatin remodeling enzymes critically involved in the regulation of multiple functions, including gene expression, differentiation, development, DNA repair, cell adhesion and cell cycle control. BRM, a key SWI/SNF complex subunit, is silenced in 15-20% of many solid tumors. As BRM-deficient mice develop 10-fold more tumors when exposed to carcinogens, BRM is a strong candidate for a cancer susceptibility gene. In this paper, we show that BRM is regulated by transcription, thus demonstrating that the promoter region is important for BRM expression. We sequenced the BRM promoter region, finding two novel promoter indel polymorphisms, BRM -741 and BRM -1321, that are in linkage disequilibrium (D'≥0.83). The variant insertion alleles of both polymorphisms produce sequence variants that are highly homologous to myocyte enhancer factor-2 (MEF2) transcription factor-binding sites; MEF2 is known to recruit histone deacetylases that silence BRM expression. Each polymorphic BRM insertion variant is found in ~20% of Caucasians, and each correlates strongly with the loss of protein expression of BRM, both in cancer cell lines (P=0.009) and in primary human lung tumor specimens (P=0.015). With such strong functional evidence, we conducted a case-control study of 1199 smokers. We found an increased risk of lung cancer when both BRM homozygous promoter insertion variants were present: adjusted odds ratio of 2.19 (95% confidence interval, 1.40-3.43). Thus, we here demonstrate a strong functional association between these polymorphisms and loss of BRM expression. These polymorphisms thus have the potential to identify a sub-population of smokers at greater lung cancer risk, wherein this risk could be driven by an aberrant SWI/SNF chromatin-remodeling pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.