Investigation of Hotspot Mutations in PI3K (PIK3CA) Gene in Iranian Women with Triple Negative and Non Triple Negative Breast Cancer

Introduction: PI3K is a heterodimeric enzyme composed of a p110a catalytic subunit encoded by the PIK3CA gene and a p85 regulatory subunit encoded by the PIK3R1 gene. Phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit a (PIK3CA) is a central element of a signaling pathway involved in cell proliferation, survival, and growth.Certain mutations in this pathway result in enhanced PI3K signaling, which is associated with oncogenic cellular transformation and cancer. Gain of function mutations inPIK3CA have been found in several cancers, including breast cancer. PIK3CA is frequently mutated at ‘hotspots’ in exons 9 and 20, corresponding to the helical (E542K and E545K) and kinase (H1047R) domains. 30-40 % of breast cancers have mutation in this gene, and 90% of them are located in these three hotspots. Purpose: We examined the mutations of PIK3CA in Iranian women with Triple Negative and Non Triple Negative Breast cancer, in order to find out the frequency of PIK3CA mutation in this population.Methods/Materials: DNA samples were extracted from paraffin embedded tumor tissue blocks. Primers were designed for hotspot mutations in exon 9 and 20.target exons were amplified with PCR and mutations were evaluated by Sanger Sequencing Technique .results were analyzed by codoncode aligner software. Results: overly 32 cases from 38 cases were detected with mutation in PIK3CA. 2 of them had just H1047R A> T,23 cases had E545A A> C, one of them had both E542K G> A and E545A A> C and 6 cases had both H1047R A> T and E545A A> C. and no cases had E545K mutation. Discussion: Our study shows difference in the frequency and type of mutations between our population and the other. This difference could be due to variability within populations, race and environmental factors.

Keywords:

PIK3CA , breast cancer , PCR , Sanger Sequencing