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Published on: June 9, 2023
Phosphatidylinositol 3-kinase (PI3KCA) oncogene mutation analysis and gene expression profiling in primary breast
Mahesh Kandula1, Kalyan Kumar Chennaboina, Ammi Raju Ys
1Department of Biotechnology, Krisani Biosciences Private Limited, India
Background:
The phosphatidylinositol 3-kinase (PI3K) pathway plays a significant role in apoptosis, cellular proliferation and motility. The aim of the present study was to analyze mutations and gene expression profiles of the PI3KCA gene to determine any role in breast carcinomas.
Materials And Methods:
We analyzed 38 breast cancers for mutations in the two PIK3CA hotspots in exons 9 and 20 by direct sequencing of DNA obtained from biopsy samples. We have also analyzed expression of the PI3KCA gene in 38 breast carcinoma tumor and corresponding control tissue samples at the mRNA level by RT-PCR. The Fisher's exact test (2?2 only) was performed using MedCalc software for to examine associations with mRNA levels.
Results:
In the present study a total of 13 cases demonstrated somatic mutations. In 9/13 cases 1633 G>A (E545K) were found in exon 9, whereas in exon 20, 4/13 cases had 3140A>G mutation. Our combined analysis showed PI3KCA mutations present in 34% of human breast cancer patients. In our study, we have also clearly found significantly higher expression in breast cancer tissues in comparison with control tissues (p=0.001).
Conclusions:
PIK3CA mutation is an emerging tumor marker that, in the future, might be used in the process of choosing a treatment. The detection of PI3KCA mutation might have important clinical implications for diagnosis, progression and therapy.
Insights
Mutations in the PIK3CA gene were found in 34% of breast cancers, with higher gene expression in tumor tissues. PIK3CA mutation detection may aid in breast cancer diagnosis and treatment selection.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The phosphatidylinositol 3-kinase (PI3K) pathway is crucial for cell apoptosis, proliferation, and motility.
- Investigating the PIK3CA gene's role in breast carcinomas is essential for understanding cancer development.
Purpose of the Study:
- To analyze mutations and gene expression profiles of the PIK3CA gene in breast carcinomas.
- To determine the potential role of PIK3CA alterations in breast cancer.
Main Methods:
- Direct DNA sequencing of PIK3CA hotspots (exons 9 and 20) in 38 breast cancer biopsy samples.
- Quantitative analysis of PIK3CA gene expression at the mRNA level using RT-PCR in tumor and control tissues.
- Statistical analysis using Fisher's exact test to correlate mRNA levels.
Main Results:
- Somatic mutations in PIK3CA were identified in 13 out of 38 cases (34% of patients).
- Specific mutations found include G>A (E545K) in exon 9 (9/13 cases) and A>G in exon 20 (4/13 cases).
- Significantly higher PIK3CA mRNA expression was observed in breast cancer tissues compared to control tissues (p=0.001).
Conclusions:
- PIK3CA mutations are prevalent in breast cancer and represent a potential emerging tumor marker.
- Detection of PIK3CA mutations may hold significant clinical implications for breast cancer diagnosis, progression monitoring, and therapeutic strategy.
- Future applications may include utilizing PIK3CA mutation status to guide treatment selection.
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