RGD Reference Report - Loss of the SWI/SNF-ATPase subunit members SMARCF1 (ARID1A), SMARCA2 (BRM), SMARCA4 (BRG1) and SMARCB1 (INI1) in oesophageal adenocarcinoma. - Rat Genome Database

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Loss of the SWI/SNF-ATPase subunit members SMARCF1 (ARID1A), SMARCA2 (BRM), SMARCA4 (BRG1) and SMARCB1 (INI1) in oesophageal adenocarcinoma.

Authors: Schallenberg, Simon  Bork, Julian  Essakly, Ahlem  Alakus, Hakan  Buettner, Reinhard  Hillmer, Axel M  Bruns, Christiane  Schroeder, Wolfgang  Zander, Thomas  Loeser, Heike  Gebauer, Florian  Quaas, Alexander 
Citation: Schallenberg S, etal., BMC Cancer. 2020 Jan 6;20(1):12. doi: 10.1186/s12885-019-6425-3.
RGD ID: 127285649
Pubmed: PMID:31906887   (View Abstract at PubMed)
PMCID: PMC6945480   (View Article at PubMed Central)
DOI: DOI:10.1186/s12885-019-6425-3   (Journal Full-text)


BACKGROUND: The SWI/SNF complex is an important chromatin remodeler, commonly dysregulated in cancer, with an estimated mutation frequency of 20%. ARID1A is the most frequently mutated subunit gene. Almost nothing is known about the other familiar members of the SWI/SNF complexes, SMARCA2 (BRM), SMARCA4 (BRG1) and SMARCB1 (INI1), in oesophageal adenocarcinoma (EAC).
METHODS: We analysed a large cohort of 685 patients with EAC. We used four different antibodies to detect a loss-of-protein of ARID1A BRM, BRG1 and INI1 by immunohistochemistry and correlated these findings with molecular and clinical data.
RESULTS: Loss of ARID1A, BRG1, BRM and INI1 was observed in 10.4, 3.4, 9.9 and 2% of EAC. We found a co-existing protein loss of ARID1A and BRM in 9.9% and of ARID1A and BRG1 in 2.2%. Patients with loss of ARID1A and TP53 wildtype EACs showed a shortened overall survival compared with AIRDA1A-positive tumours [median overall survival was 60.1 months (95%CI 1.2-139.9 months)] in patients with ARIDA-1A expression and 26.2 months (95%CI 3.7-19.1 months) in cases of ARIDA-1A loss (p = 0.044). Tumours with loss or expression of ARID1A and TP53 loss were not associated with a difference in survival. Only one tumour revealed high microsatellite instability (MSI-H) with concomitant ARID1A loss. All other ARID1A loss-EACs were microsatellite-stable (MSS). No predictive relevance was seen for SWI/SNF-complex alterations and simultaneous amplification of different genes (PIK3CA, KRAS, c-MYC, MET, GATA6, ERBB2).
CONCLUSION: Our work describes, for the first time, loss of one of the SWI/SNF ATPase subunit proteins in a large number of adenocarcinomas of the oesophagus. Several papers discuss possible therapeutic interventions for tumours showing a loss of function of the SWI/SNF complex, such as PARP inhibitors or PI3K and AKT inhibitors. Future studies will be needed to show whether SWI/SNF complex-deficient EACs may benefit from personalized therapy.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ARID1AHumanesophagus adenocarcinoma disease_progressionIEP  RGD 
Arid1aRatesophagus adenocarcinoma disease_progressionISOARID1A (Homo sapiens) RGD 
Arid1aMouseesophagus adenocarcinoma disease_progressionISOARID1A (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Arid1a  (AT-rich interaction domain 1A)

Genes (Mus musculus)
Arid1a  (AT-rich interaction domain 1A)

Genes (Homo sapiens)
ARID1A  (AT-rich interaction domain 1A)


Additional Information