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Characterization of Small Genetic Variants in Breast Cancer Cell Line Under Tamoxifen Therapy
Mahnaz Nezamivand-Chegini1, Hamed Kharrati-Koopaee1, Seyed Taghi Heydari2
1Institute of Biotechnology, Shiraz University, Shiraz, Iran.
Background:
Tamoxifen (TAM) is an effective hormone therapy in order to reduce the risk of cancer recurrence. According to the available findings, TAM contributes to the alterations of genetic variants background and may have role in the effectiveness of treatments via alteration of the genetic variants. The effects of TAM on genomic features were investigated in current study through discovering genetic variants and finding the answer of the following question: "Is there any association between the alterations of genetic variants under TAM consumption and an effective treatment process?"
Materials And Methods:
Whole-transcriptome (RNA-seq) dataset of four investigations including 10 TAM-treated samples and 9 untreated samples as the control groups were derived from European Bioinformatics Institute (EBI). Using the process of variants calling, the differential genetic variants between and gene ontology enrichment analysis were detected through CLC Genomics Workbench (12).
Results:
In current study, almost 5.8 million genetic variants were reported. The outcomes of chi-square test showed that distributions of genetic variants between control and treated samples were significant (P0.05). The genetic variants comparison between the control and TAM-treated samples indicated that there were 67 differential genetic variants. Gene ontology enrichment analysis indicated that differential genetic variants were associated with several tumor suppressors and oncogenes such as IL6ST, GEN1, FNTA. HSPA5, NSMCE2, and DDX11.
Conclusion:
Most of the candidate genes with differential genetic variants had dual roles as oncogenes or tumor suppressors. Therefore, it can be claimed that TAM has no significant role in an effective treatment through alteration of the genetic variants. In other words, it cannot be concluded that the TAM therapy-resulted alterations of genetic variants have positive or negative roles in the treatment process.
Insights
Tamoxifen (TAM) therapy may alter genetic variants, but this study found no significant association between these alterations and treatment effectiveness. Further research is needed to clarify TAM's role in cancer treatment outcomes.
Area of Science:
- Genomics
- Oncology
- Pharmacogenomics
Background:
- Tamoxifen (TAM) is a crucial hormone therapy for reducing cancer recurrence.
- TAM's influence on genetic variants and its potential role in treatment efficacy require investigation.
Purpose of the Study:
- To investigate the effects of TAM on genomic features.
- To determine if TAM-induced genetic variant alterations are associated with effective cancer treatment.
Main Methods:
- Whole-transcriptome sequencing (RNA-seq) data from TAM-treated and untreated samples were analyzed.
- Variant calling and gene ontology enrichment analysis were performed using CLC Genomics Workbench.
Main Results:
- Approximately 5.8 million genetic variants were identified.
- 67 differential genetic variants were found between TAM-treated and control groups.
- Enrichment analysis linked these variants to key oncogenes and tumor suppressors (e.g., IL6ST, GEN1, FNTA).
Conclusions:
- Candidate genes with differential variants often possess dual oncogenic or tumor-suppressive roles.
- TAM-induced genetic variant alterations do not show a significant association with effective cancer treatment.
- The precise impact of TAM on treatment outcomes via genetic modifications remains inconclusive.
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