Related Experiment Video
Updated: May 29, 2026
Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
Published on: May 17, 2019
An integrated genomic approach identifies ARID1A as a candidate tumor-suppressor gene in breast cancer
A Mamo1, L Cavallone, S Tuzmen
1Department of Oncology, Lady Davis Institute, Sir Mortimer B Davis Jewish General Hospital, McGill University, Montreal, Québec, Canada.
Abstract:
Tumor-suppressor genes (TSGs) have been classically defined as genes whose loss of function in tumor cells contributes to the formation and/or maintenance of the tumor phenotype. TSGs containing nonsense mutations may not be expressed because of nonsense-mediated RNA decay (NMD). We combined inhibition of the NMD process, which clears transcripts that contain nonsense mutations, with the application of high-density single-nucleotide polymorphism arrays analysis to discriminate allelic content in order to identify candidate TSGs in five breast cancer cell lines. We identified ARID1A as a target of NMD in the T47D breast cancer cell line, likely as a consequence of a mutation in exon-9, which introduces a premature stop codon at position Q944. ARID1A encodes a human homolog of yeast SWI1, which is an integral member of the hSWI/SNF complex, an ATP-dependent, chromatin-remodeling, multiple-subunit enzyme. Although we did not find any somatic mutations in 11 breast tumors, which show DNA copy-number loss at the 1p36 locus adjacent to ARID1A, we show that low ARID1A RNA or nuclear protein expression is associated with more aggressive breast cancer phenotypes, such as high tumor grade, in two independent cohorts of over 200 human breast cancer cases each. We also found that low ARID1A nuclear expression becomes more prevalent during the later stages of breast tumor progression. Finally, we found that ARID1A re-expression in the T47D cell line results in significant inhibition of colony formation in soft agar. These results suggest that ARID1A may be a candidate TSG in breast cancer.
Insights
Tumor-suppressor genes (TSGs) may escape detection due to nonsense-mediated RNA decay (NMD). Researchers identified ARID1A as a potential TSG in breast cancer by inhibiting NMD, showing its low expression correlates with aggressive tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Tumor-suppressor genes (TSGs) are critical for preventing cancer, but their function can be lost through mutations.
- Nonsense-mediated RNA decay (NMD) can eliminate transcripts with premature stop codons, potentially masking TSG inactivation.
- Identifying novel TSGs is crucial for understanding cancer development and finding new therapeutic targets.
Purpose of the Study:
- To identify candidate tumor-suppressor genes (TSGs) silenced by nonsense-mediated RNA decay (NMD) in breast cancer.
- To investigate the role of ARID1A, a potential NMD target, in breast cancer progression and aggressiveness.
Main Methods:
- Combined NMD inhibition with high-density single-nucleotide polymorphism arrays to identify candidate TSGs in breast cancer cell lines.
- Analyzed ARID1A expression levels and mutations in breast cancer cell lines and patient cohorts.
- Assessed the functional impact of ARID1A re-expression on cancer cell proliferation.
Main Results:
- Identified ARID1A as an NMD target in T47D breast cancer cells, likely due to a premature stop codon mutation.
- Found that low ARID1A RNA or nuclear protein expression is associated with aggressive breast cancer phenotypes (e.g., high tumor grade) in independent cohorts.
- Observed increased prevalence of low ARID1A nuclear expression in later stages of tumor progression.
- Demonstrated that ARID1A re-expression inhibits colony formation in soft agar, suggesting a tumor-suppressive role.
Conclusions:
- ARID1A is a candidate tumor-suppressor gene (TSG) in breast cancer, potentially inactivated through NMD.
- Loss of ARID1A expression correlates with aggressive tumor features and advanced stages of breast cancer.
- ARID1A re-expression exhibits anti-proliferative effects, supporting its role in suppressing tumor formation.
Related Concept Videos
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...