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

Mahesh Kandula,Y.S Ammi Raju,Kalyan Kumar Chennaboina,Suryanarayana Raju

doi:10.7314/apjcp.2013.14.9.5067

Abstract

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. 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. 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). 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.

Highlights

Phosphatidylinositol 3-kinase/AKT/mTOR pathway plays an important role in proliferation, migration and survival
The PIK3CA pathway is frequently activated in different human cancers PIK3CA gene is mutated in an average of 15% of human cancers it is evident that cancer of the breast harbor the most PIK3CA mutation with average mutation frequency of 25%
In this study we have reported the presence of PIK3CA gene mutation in 28% of breast cancer tumors

Summary

Introduction

Phosphatidylinositol 3-kinase/AKT/mTOR pathway plays an important role in proliferation, migration and survival. Mutations in the PI3KCA gene play a significant role in carcinogenesis and progression which occurs in many cancers including breast cancer (Vivanco, 2002). A preclinical study has demonstrated that breast tumors with the mutations in the PI3KCA gene are resistant towards the PI3K inhibitors due to RAS/RAF/MEK pathway activation (Ihle et al, 2009). We hypothesized that mutations resulting in the activation of the PIK3CA pathway may play a role in the progression of breast cancer. To test this hypothesis, we analyzed gene expression profiles. 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. The detection of PI3KCA mutation might have important clinical implications for diagnosis, progression and therapy

Objectives

Methods

Findings

Conclusion