Detection of PIK3CA gene mutations with HRM analysis and association with IGFBP-5 expression levels in breast cancer.

Abstract

Breast cancer is the second most common cancer and second leading cause of cancer deaths in women. Phosphatidylinositol-3-kinase (PI3K)/AKT pathway mutations are associated with cancer and phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene mutations have been observed in 25-45% of breast cancer samples. Insulin growth factor binding protein-5 (IGFBP-5) can show different effects on apoptosis, cell motility and survival in breast cancer. We here aimed to determine the association between PIK3CA gene mutations and IGFBP-5 expressions for the first time in breast cancer patients. Frozen tumor samples from 101 Turkish breast cancer patients were analyzed with high resolution melting (HRM) for PIK3CA mutations (exon 9 and exon 20) and 37 HRM positive tumor samples were analyzed by DNA sequencing, mutations being found in 31. PIK3CA exon 9 mutations (Q546R, E542Q, E545K, E542K and E545D) were found in 10 tumor samples, exon 20 mutations (H1047L, H1047R, T1025T and G1049R) in 21, where only 1 tumor sample had two exon 20 mutations (T1025T and H1047R). Moreover, we detected one sample with both exon 9 (E542Q) and exon 20 (H1047R) mutations. 35% of the tumor samples with high IGFBP-5 mRNA expression and 29.4% of the tumor samples with low IGFBP-5 mRNA expression had PIK3CA mutations (p=0.9924). This is the first study of PIK3CA mutation screening results in Turkish breast cancer population using HRM analysis. This approach appears to be a very effective and reliable screening method for the PIK3CA exon 9 and 20 mutation detection. Further analysis with a greater number of samples is needed to clarify association between PIK3CA gene mutations and IGFBP-5 mRNA expression, and also clinical outcome in breast cancer patients.

• Authors: Ebubekir Dirican, Zehra Kaya, Gokce Gullu, Irem Peker, Tolga Ozmen, Bahadir M Gulluoglu, Handan Kaya, Ayse Ozer, Mustafa Akkiprik
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 15 Issue 21 Pg. 9327-33 ( 2014) ISSN: 2476-762X [Electronic] Thailand
• PMID: 25422220 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin-Like Growth Factor Binding Protein 5
• Phosphatidylinositol 3-Kinases
• Class I Phosphatidylinositol 3-Kinases
• PIK3CA protein, human

Topics

• Adult
• Aged
• Aged, 80 and over
• Biopsy, Needle
• Breast Neoplasms (genetics, mortality, pathology)
• Class I Phosphatidylinositol 3-Kinases
• Disease Progression
• Early Detection of Cancer (methods)
• Female
• Frozen Sections
• Gene Expression Regulation, Neoplastic
• Genetic Association Studies
• Humans
• Insulin-Like Growth Factor Binding Protein 5 (genetics)
• Kaplan-Meier Estimate
• Middle Aged
• Mutation (genetics)
• Neoplasm Invasiveness (pathology)
• Neoplasm Staging
• Phosphatidylinositol 3-Kinases (genetics)
• Polymerase Chain Reaction (methods)
• Predictive Value of Tests
• Prognosis
• Proportional Hazards Models
• Restriction Mapping (methods)
• Risk Assessment
• Sequence Analysis, DNA (methods)
• Statistics, Nonparametric
• Survival Rate
• Turkey