Detection of PIK3CA Gene Mutations with HRM Analysis and Association with IGFBP-5 Expression Levels in Breast Cancer

Dirican, Ebubekir; Kaya, Zehra; Gullu, Gokce; Peker, Irem; Ozmen, Tolga; Gulluoglu, Bahadir M.; Kaya, Handan; Ozer, Ayse; Akkiprik, Mustafa

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자료유형: 학술저널

저자정보: Dirican, Ebubekir (Department of Medical Biology, School of Medicine, Marmara University) Kaya, Zehra (Department of Medical Biology, School of Medicine, Marmara University) Gullu, Gokce (Department of Medical Biology, School of Medicine, Marmara University) Peker, Irem (Department of Medical Biology, School of Medicine, Marmara University) Ozmen, Tolga (Department of General Surgery, School of Medicine, Marmara University) Gulluoglu, Bahadir M. (Department of General Surgery, School of Medicine, Marmara University) Kaya, Handan (Department of Pathology, School of Medicine, Marmara University) Ozer, Ayse (Department of Medical Biology, School of Medicine, Marmara University) Akkiprik, Mustafa (Department of Medical Biology, School of Medicine, Marmara University)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제15권 제21호

발행연도: 2014.1

수록면: 9,327 - 9,333 (7page)

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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.

#PIK3CA #PI3K #IGFBP5 #HRM assay #Turkish breast cancer #mutation

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