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Analysis of PIK3CA mutations and activation pathways in triple negative breast cancer

Cossu Rocca, Paolo Alessandro and Orrù, Sandra and Muroni, Maria Rosaria and Sanges, Francesca and Sotgiu, Giovanni and Ena, Sara and Piras, Giovanna and Murgia, Luciano and Manca, Alessandra and Uras, Maria Gabriela and Sarobba, Maria Giuseppa and Urru, Silvana and De Miglio, Maria Rosaria (2015) Analysis of PIK3CA mutations and activation pathways in triple negative breast cancer. PLoS One, Vol. 10 (11), e0141763. ISSN 1932-6203. Article.

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DOI: 10.1371/journal.pone.0141763

Abstract

Background: Triple Negative Breast Cancer (TNBC) accounts for 12–24% of all breast carcinomas, and shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated that TNBCs are a heterogeneous group of tumors with different clinical and pathologic features, prognosis, genetic-molecular alterations and treatment responsivity. The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes. The most common genetic abnormality is represented by PIK3CA gene activating mutations, with an overall frequency of 20–40%. The aims of our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways and to correlate the results with clinical-pathologic data.
Materials and Methods: PIK3CA mutation analysis was performed by using cobas® PIK3CA Mutation Test. EGFR, AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components.
Results: PIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT and p-p44/42 MAPK in all PIK3CA mutated TNBC.
Conclusions: Our data shows that PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be helpful in order to select patients who would benefit from current targeted therapy strategies.

Item Type:Article
ID Code:11748
Status:Published
Refereed:Yes
Uncontrolled Keywords:Mutation, mutation detection, cancer treatment, MAPK signaling cascades, mutational analysis, breast cancer, histology, cancer genomics
Subjects:Area 06 - Scienze mediche > MED/08 Anatomia patologica
Area 06 - Scienze mediche > MED/04 Patologia generale
Divisions:002 Altri enti e centri di ricerca del Nord Sardegna > AOU -Azienda Ospedaliero Universitaria, Sassari
001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Medicina Clinica e Sperimentale
Publisher:Public Library of Science
ISSN:1932-6203
Copyright Holders:© 2015 Cossu-Rocca et al.
Deposited On:12 Jun 2017 12:55

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