Evidence map›Paper›PMID 27486753›Full record

ArticleOncotarget2016

Mechanism of BRG1 silencing in primary cancers.

Stefanie B Marquez-Vilendrer, Kenneth Thompson, Li Lu, David Reisman

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. RNA-Seq Profiling Reveals Transcriptional Changes in Phosphorylation-Site Mutants of Brg1.Genes to cells : devoted to molecular & cellular mechanisms · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Stefanie B Marquez-VilendrerDivision of Hematology/Oncology, Department of Medicine, University of Florida, Gainesville, Florida, USA.
Kenneth ThompsonDivision of Hematology/Oncology, Department of Medicine, University of Florida, Gainesville, Florida, USA.
Li LuDepartment of Pathology, University of Florida, Gainesville, Florida, USA.
David ReismanDivision of Hematology/Oncology, Department of Medicine, University of Florida, Gainesville, Florida, USA.
University of Florida · US

Funding

Impact of BRG1 Loss in Lung Cancer DevelopmentR01CA127636 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI REISMAN, DAVID N · 2007 to 2012
$1.4M
Identifying Agents which Restored BRM expressionR01CA136683 · NCI · UNIVERSITY OF FLORIDA · PI REISMAN, DAVID N · 2010 to 2013
$877k
NCI NIH HHS R01 CA127636NCI NIH HHS R01 CA136683
6 · The paper itself

Abstract

BRG1 (SMARCA4) is a documented tumor suppressor and a key subunit of the SWI/SNF chromatin remodeling complex that is silenced in many cancer types. Studies have shown that BRG1 is mutated in cancer-derived cell lines, which led to the assertion that BRG1 is also mutated in primary human tumors. However, the sequencing of BRG1-deficient tumors has revealed a paucity of mutations; hence, the cause of BRG1 silencing in tumors remains an enigma. We conducted immunohistochemistry (IHC) on a number of tumor microarrays to characterize the frequency of BRG1 loss in different tumor types. We also analyzed BRG1-deficient tumors by sequencing the genomic DNA and the mRNA. We then tested if BRG1 expression could be induced in BRG1-negative cell lines (i.e., that lack mutations in BRG1) after the application of several different epigenetic agents, including drugs that inhibit the AKT pathway. We found that a subset of BRG1-negative cell lines also demonstrated aberrant splicing of BRG1, and in at least 30% of BRG1-deficient tumors, BRG1 expression appeared to be suppressed due to aberrant BRG1 splicing. As the majority of BRG1-deficient tumors lack mutations or splicing defects that could drive BRG1 loss of expression, this suggests that other mechanisms underlie BRG1 silencing. To this end, we analyzed 3 BRG1-deficient nonmutated cancer cell lines and found that BRG1 was inducible in these cell lines upon inhibition of the AKT pathway. We show that the loss of BRG1 is associated with the loss of E-cadherin and up-regulation of Vimentin in primary tumors, which explains why BRG1 loss is associated with a poor prognosis in multiple tumor types.

Indexed as

Gene Expression Regulation, NeoplasticGene SilencingGenes, Tumor SuppressorAntigens, CDCadherinsCell Line, TumorChromatin Assembly and DisassemblyDNA HelicasesHumansImmunohistochemistryMutationNeoplasmsNuclear ProteinsPrognosisProto-Oncogene Proteins c-aktRNA, MessengerAntigens, CDCadherinsCDH1 protein, humanDNA HelicasesNuclear ProteinsProto-Oncogene Proteins c-aktRNA, MessengerSMARCA4 protein, humanTranscription FactorsVimentinBRG1cancerepigeneticmutationSWI/SNF

Identifiers

PMID27486753
PMCPMC5302903
OpenAlexW2463141307

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.