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Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Detection of PIK3/AKT pathway in Moroccan population with triple negative breast cancer
Farah Jouali1,2, Nabila Marchoudi3, Salwa Talbi4
1Anoual Laboratory of Radio-Immuno Analysis, Angle Blvd Alexandrieet Blvd Anoual, 20360, Casablanca, Morocco. frh_0712@hotmail.com.
Background:
Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer, that represents 10-20% of all breast carcinomas and characterized by the lack of a specific cell surface marker compared to other breast cancer subtypes. Due to the absence of molecular markers for TNBC his treatment options remains limited, without proven targeted therapies, which emphasize the need for discovering molecular markers that could be targeted for patient treatment, An important number of TNBC cases harbor aberrations in the phosphoinositide 3-kinase (PI3K) pathway, leading to constitutive activation of the downstream signaling pathway. Among mechanisms of PI3K enhancement, PIK3CA mutations are most frequently (~ 30%) observed, along with protein loss of PTEN and AKT activation by phosphorylation (pAkt). Therefore, we propose to analyze clinocopathologic and molecular characteristics of PI3K/AKT/PTEN pathway in Moroccan triple negative breast cancer patients.
Methods:
We conducted a retrospective study of 39 patients diagnosed with triple negative breast cancer between early 2013 and 2016. In this study, we used the Ion Personal Genome Machine (PGM) and Ion Torrent Ampliseq Cancer panel to sequence hotspot regions from PIK3CA, AKT and PTEN genes to identify genetic mutations in 39 samples of TNBC subtype from Moroccan patients and to correlate the results with clinical-pathologic data.
Results:
All patients were female with a median age of 46 years from (34-65). Most patients have had invasive ductal carcinoma (84.6%) and 69.2% of them were grade III SBR. Among the 39, 9 were right sided tumor patients and the remaining 30 were left-sided. Mutational analysis of PIK3CA gene was achieved in all TNBC patients. PIK3CA hotspot mutations were detected in 5/39 of TNBC (13%), in detail, among these 5 TNBC patients, one harbored mutation in exons 9 and four in exon 20.
Conclusion:
The PI3KCA gene is highly activated and plays a crucial role in the pathogenesis of TNBC more, therefore, may be a potential therapeutic target to improve outcomes in patients.
Insights
Mutations in the PIK3CA gene are common in triple-negative breast cancer (TNBC). Identifying these PIK3CA mutations offers potential therapeutic targets for TNBC patients, improving treatment outcomes.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) lacks specific cell surface markers, leading to limited treatment options.
- The phosphoinositide 3-kinase (PI3K) pathway is frequently aberrant in TNBC, often due to PIK3CA mutations.
- Understanding TNBC molecular characteristics is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the clinocopathologic and molecular features of the PI3K/AKT/PTEN pathway in Moroccan TNBC patients.
- To identify genetic mutations in PIK3CA, AKT, and PTEN genes within a cohort of Moroccan TNBC.
- To correlate genetic findings with clinical-pathologic data in TNBC.
Main Methods:
- Retrospective analysis of 39 Moroccan TNBC patients diagnosed between 2013 and 2016.
- Sequencing of hotspot regions in PIK3CA, AKT, and PTEN genes using Ion Personal Genome Machine (PGM) and Ion Torrent Ampliseq Cancer panel.
- Correlation of identified genetic mutations with available clinical-pathologic information.
Main Results:
- The study included 39 female patients with a median age of 46 years.
- Most cases were invasive ductal carcinoma (84.6%) and grade III SBR (69.2%).
- PIK3CA hotspot mutations were identified in 13% (5/39) of TNBC patients, with mutations found in exons 9 and 20.
Conclusions:
- The PIK3CA gene is frequently activated in TNBC, highlighting its significant role in disease pathogenesis.
- PIK3CA mutations represent a potential therapeutic target for improving outcomes in triple-negative breast cancer.
- Further research into PI3K pathway alterations can guide targeted treatment strategies for TNBC.
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