The Mutational Hotspots Of PIK3CA In Breast Cancer

Background and ObjectivePIK3CA gene plays a role as an oncogene in many kinds of tumors. The protein named phosphatidylinositol 3-kinases (PI3K) which is encoded by PIK3CA plays an important role in cell growth, apoptosis and tumor formation. The functional and genetics research shows that PIK3CA gene is an oncogene. PIK3CA mutations are exist in many kinds of solid tumor in human. Recent researches showed frequent somatic mutations of PIK3CA were found in many kinds of tumor including colon cancer, ovarian cancer, breast cancer, gastric cancer and liver cancer. PIK3CA gene mutation is a key step of the oncogenesis and development of many solid tumors. The mutation causes PI3K pathway abnormality in different level, then finally promotes cell growth and proliferation, inhibits cell apoptosis, and induce to oncogenesis.PIK3CA mutations are among the most commonly mutated genes identified in breast cancer. Frequency of PIK3CA mutations in breast cancer ranges from 8-40%. 80-90% of these mutations occur in exons 9 and 20, corresponding to the helical and kinase domains. These nonrandom and high frequency mutations reveal their significance in oncogenesis.The frequency of most Single nucleotide polymorphism (SNP) is significant deviation in different population, and the reports of the mutation of PIK3CA in breast cancer among Chinese women are rare seen at present. So this study was designed to investigate the two mutational hotspots in exon 9 and exon 20 of PIK3CA gene in breast cancer among Chinese women, and the association of the mutation and the pathological features of breast cancer.Materials and Methods1. Sample collection: 45 frozen tissues of primary breast cancer were collected from Changhai Hospital between January 2006 and July 2006. The tissues were stored at -80℃. All the cases were confirmed by operation and pathology. Other 10 frozen tissues of benign breast tumor were obtained as control. Informed consent were obtained.2. Experimental Design: PCR amplification of exons 9 and 20 was done after extracting DNA from 45 samples of breast cancer, followed by sequencing after the product was purified. Other 10 samples of benign breast tumor were also sequenced as controls.3. Statistical analysis: Using SPSS 13.0 software. Probability values less than 0.05 were considered to indicate statistical significance.Results1. We found 14(31%) missense mutations, 8(57%) in exon 9, 6(43%) in exon 20. In eight cases of exon 9, 1 was C1616G (P539R), 1 was G1633A (E545K), 6 were A1634C (E545A).All 6 cases of mutations in exon 20 were A3140G (H1047R). No mutation was found in 10 cases of benign breast tumor.2. There was no significant difference in the distribution of mutation in invasive ductal carcinoma and invasive lobular carcinoma in both exon 9 and exon 20. The mutation of PIK3CA gene has no significant correlation with age, tumor size, lymph node status, ER / PR status, HER2 expression, P53 expression.Conclusion1. In this study, we confirm the high frequency of PIK3CA mutations in human breast cancer among Chinese women, occurring in 31% of our cases, in keeping with literature data before. Indicate PIK3CA gene may be associated with development and prognosis of breast cancer.2. There was no significant correlation between PIK3CA gene mutation and the pathological feature of breast cancer such as patient age, tumor size, nodal status, ER and PR status, Her2/neu overexpression and P53 expression.