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Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Aurora-A gene is frequently amplified in basal-like breast cancer
Synnöve Staff1, Jorma Isola, Mervi Jumppanen
1Institute of Medical Technology, University and University Hospital of Tampere, Tampere, Finland. synnove.staff@uta.fi
Abstract:
Aurora-A is a serine-threonine kinase having vital cellular functions in mitosis and is a promising target for therapy in treating patients with cancer. This study assesses the clinicopathological associations of AURKA gene amplification in clinical breast tumors and association of gene copy number with its mRNA and protein expression in breast cancer cell lines. In this pilot study, we examined Aurora-A gene (AURKA) amplification in 126 clinical breast tumors by chromogenic in situ hybridisation (CISH). AURKA amplification (found in 21%) showed an association with basal-like tumor phenotype (p=0.046). A separate series of basal-like breast tumors (n=26) provided further evidence of the importance of AURKA in these tumors. AURKA amplification status was associated with immunohistochemically detectable Aurora-A protein expression (p<0.0001). In breast cancer cell lines, gene amplification was strongly associated with high mRNA expression (p<0.0001). JIMT-1 cell line was found as a possible in vitro model system for testing Aurora-A inhibitors, since it has been classified as basal-like breast cancer and here it showed both AURKA gene amplification and elevated mRNA expression. AURKA gene amplification is a common genetic aberration in breast cancer, especially in tumors displaying basal-like phenotype. Thus, these patients might be suitable candidates for future targeted therapies with Aurora-A inhibitors.
Insights
Aurora-A kinase (AURKA) gene amplification is common in breast cancer, particularly in basal-like tumors. This finding suggests patients with AURKA amplification may benefit from targeted Aurora-A inhibitor therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Aurora-A kinase (AURKA) plays a critical role in mitosis.
- AURKA is a potential therapeutic target for cancer treatment.
- Understanding AURKA gene alterations in breast cancer is crucial for targeted therapy development.
Purpose of the Study:
- To investigate the clinicopathological associations of AURKA gene amplification in clinical breast tumors.
- To correlate AURKA gene copy number with its mRNA and protein expression in breast cancer cell lines.
- To identify potential in vitro models for evaluating Aurora-A inhibitors.
Main Methods:
- Chromogenic in situ hybridisation (CISH) was used to examine AURKA gene amplification in 126 clinical breast tumors.
- Immunohistochemistry was employed to assess Aurora-A protein expression.
- Gene amplification, mRNA, and protein expression levels were analyzed in breast cancer cell lines.
Main Results:
- AURKA amplification was detected in 21% of breast tumors and associated with a basal-like phenotype (p=0.046).
- AURKA amplification correlated significantly with increased Aurora-A protein expression (p<0.0001).
- In cell lines, gene amplification strongly associated with high mRNA expression (p<0.0001), with JIMT-1 identified as a suitable model.
Conclusions:
- AURKA gene amplification is a frequent genetic alteration in breast cancer, especially in basal-like subtypes.
- Patients with AURKA-amplified basal-like breast tumors may be candidates for Aurora-A inhibitor therapy.
- The JIMT-1 cell line serves as a valuable in vitro model for preclinical studies of Aurora-A inhibitors.
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