ABSTRACT
PURPOSE: Mutations of the PI3K/AKT/mTOR signaling pathway occur in 70% of all breast cancers and represent a clinically useful marker for disease prognosis and patient management. The purpose of this work was to study the main somatic PIK3CA gene mutations in breast cancer patients and the search for a relationship with the main clinical and pathological characteristics and the effect of neoadjuvant chemotherapy (NAC). METHODS: The study involved 29 patients with luminal B breast cancer. DNA was isolated from samples of tumor tissue before and after treatment using the QIAamp DNA mini Kit (Qiagen, Germany). Samples were prepared for sequencing by amplification with primers containing TruSeq index and adapter sequences (Illumina, USA) using Encyclo polymerase. RESULTS: We found 5 different somatic changes in 28% of patients: c.3140A> G (p.His1047Arg), c.3140A> T (p.His1047Leu), c.1624G> A (p.Glu542Lys), c.1633G> A ( p.Glu545Lys), c.3145G> C (p.Gly1049Arg). In the group of patients with mutations, 50% showed PIK3CA gene amplifications. The c.3140A> T (p.His1047Leu) mutation was associated with low disease-free survival rates. PIK3CA gene mutations were observed in 38% of patients with HER2-subtype, and metastasis-free survival rates were, on average, 1.5 times higher than in patients with normal gene status.
Subject(s)
Breast Neoplasms/genetics , Class I Phosphatidylinositol 3-Kinases/genetics , Mutation , Adult , Aged , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Female , Humans , Middle Aged , Neoadjuvant TherapyABSTRACT
PURPOSE: Currently, more researchers are attracted by the possibility of assessing the sensitivity of a lung tumor to certain chemotherapy drugs and their personalized choice based on an assessment of this sensitivity. The purpose of this study was to explore the prognostic significance of the level of 8 chemosensitivity genes' expression in patients with non-small cell lung cancer (NSCLC). METHODS: The study included 59 patients with NSCLC IIB-IIIA stage. RNA was isolated from the surgical material of the tumor and normal lung tissue. The expression level of 8 chemosensitivity genes BRCA1, RRM1, ERCC1, TOP1, TOP2a, TUBB3, TYMS, GSTP1 was evaluated using RT-PCR. RESULTS: Cases with higher metastasis-free survival rates showed a significantly low level of expression of the ERCC1, BRCA1, GSTP1 genes (p=0.0004, p=0.01, p=0.01). In addition, analysis of the overall survival revealed that the highest rates were achieved in patients with overexpression of the ERCC1 gene. The overall survival in these patients was 86%, versus 55% in the other group and the differences were statistically significant (p=0.002). No statistically significant differences were found for the remaining genes. CONCLUSION: Thus, a comprehensive assessment of the chemosensitivity genes expression is important not only from the point of view of understanding the heterogeneity and complexity in the field of molecular biology of NSCLC, but also for a more accurate prognosis and course of the disease.
