SLC46A1 Haplotype with Predicted Functional Impact has Prognostic Value in Breast Carcinoma
| Autor: | Viktor Hlavac, Pavel Soucek, Radka Vaclavikova, David Vrána, Veronika Brynychova, Pavel Dvorak, J Gatek, Karel Rauš, Katerina Elsnerova, Katerina Kopeckova, Renata Kozevnikovova, Sona Mestakova |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
In silico Organic Anion Transporters Breast Neoplasms Biology Real-Time Polymerase Chain Reaction 03 medical and health sciences 0302 clinical medicine Breast cancer Biomarkers Tumor Genetics medicine Humans Genetic variability Gene Pharmacology Haplotype Genetic Variation High-Throughput Nucleotide Sequencing Sequence Analysis DNA General Medicine Prognosis medicine.disease Survival Analysis Solute carrier family Gene Expression Regulation Neoplastic Minor allele frequency 030104 developmental biology Haplotypes 030220 oncology & carcinogenesis Cancer research Molecular Medicine Female Breast carcinoma Proton-Coupled Folate Transporter |
| Zdroj: | Molecular Diagnosis & Therapy. 25:99-110 |
| ISSN: | 1179-2000 1177-1062 |
| DOI: | 10.1007/s40291-020-00506-2 |
| Popis: | Membrane solute carrier transporters play an important role in the transport of a wide spectrum of substrates including anticancer drugs and cancer-related physiological substrates. This study aimed to assess the prognostic relevance of gene expression and genetic variability of selected solute carrier transporters in breast cancer. Gene expression was determined by quantitative real-time polymerase chain reaction. All SLC46A1 and SLCO1A2 exons and surrounding non-coding sequences in DNA extracted from the blood of patients with breast cancer (exploratory phase) were analyzed by next-generation sequencing technology. Common variants (minor allele frequency ≥ 5%) with in silico-predicted functional relevance were further analyzed in a large cohort of patients with breast cancer (n = 815) and their prognostic and predictive potential was estimated (validation phase). A gene expression and bioinformatics analysis suggested SLC46A1 and SLCO1A2 to play a putative role in the prognosis of patients with breast cancer. In total, 135 genetic variants (20 novel) were identified in both genes in the exploratory phase. Of these variants, 130 were non-coding, three missense, and two synonymous. One common variant in SLCO1A2 and four variants in SLC46A1 were predicted to be pathogenic by in silico programs and subsequently validated. A SLC46A1 haplotype block composed of rs2239911-rs2239910-rs8079943 was significantly associated with ERBB2/HER2 status and disease-free survival of hormonally treated patients. This study revealed the prognostic value of a SLC46A1 haplotype block for breast cancer that should be further studied. |
| Databáze: | OpenAIRE |
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