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

Asian Pac J Cancer Prev. 2014;15(21):9327-33. doi: 10.7314/apjcp.2014.15.21.9327.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy, Needle
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / 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

Substances

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