Phosphatidylinositol 3-kinase (PI3KCA) Oncogene Mutation Analysis and Gene Expression Profiling in Primary Breast Cancer Patients

Abstract

<b>Background:</b> The phosphatidylinositol 3-kinase (PI3K) pathway plays a significant role in apoptosis, cellularproliferation and motility. The aim of the present study was to analyze mutations and gene expression profilesof the PI3KCA gene to determine any role in breast carcinomas. Materials and <br/><b>Methods</b>: We analyzed 38 breastcancers for mutations in the two PIK3CA hotspots in exons 9 and 20 by direct sequencing of DNA obtainedfrom biopsy samples. We have also analyzed expression of the PI3KCA gene in 38 breast carcinoma tumor andcorresponding control tissue samples at the mRNA level by RT-PCR. The Fisher’s exact test (252 only) wasperformed using MedCalc software for to examine associations with mRNA levels. <br/><b>Results</b>: In the present study atotal of 13 cases demonstrated somatic mutations. In 9/13 cases 1633 G>A (E545K) were found in exon 9, whereasin exon 20, 4/13 cases had 3140A>G mutation. Our combined analysis showed PI3KCA mutations present in34% of human breast cancer patients. In our study, we have also clearly found significantly higher expressionin breast cancer tissues in comparison with control tissues (p=0.001). <br/><b>Conclusions</b>: PIK3CA mutation is anemerging tumor marker that, in the future, might be used in the process of choosing a treatment. The detectionof PI3KCA mutation might have important clinical implications for diagnosis, progression and therapy.