ArticlePloS one2017
Integrated analysis of promoter mutation, methylation and expression of AKT1 gene in Chinese breast cancer patients.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- The Biological Roles and Clinical Applications of the PI3K/AKT Pathway in Targeted Therapy Resistance in HER2-Positive Breast Cancer: A Comprehensive Review.International journal of molecular sciences · 2024Review
- NEBL and AKT1 maybe new targets to eliminate the colorectal cancer cells resistance to oncolytic effect of vesicular stomatitis virus M-protein.Molecular therapy oncolytics · 2021Article
- Article
- Screening of Breast Cancer Methylation Biomarkers Based on the TCGA Database.International journal of general medicine · 2021Article
- A review on methods for diagnosis of breast cancer cells and tissues.Cell proliferation · 2020Review
- Absence of Promoter Mutation in TBC1D12 Gene in Solid and Hematologic Neoplasia.Pathology oncology research : POR · 2019Article
- Promoter Mutation Analysis of ALDOA Gene in Solid Tumors and Acute Leukemias.Pathology oncology research : POR · 2019Article
- Article
- Tensor decomposition-based and principal-component-analysis-based unsupervised feature extraction applied to the gene expression and methylation profiles in the brains of social insects with multiple castes.BMC bioinformatics · 2018Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAs downstream mediators of PI3K /PTEN /AKT /mTORC1 pathway, the AKT isoforms play critical roles in tumorgenesis. Although the pleiotropic effects of AKT1 in breast cancer have been reported, the genetic and epigenetic characteristics of AKT1 promoter region in breast cancer remains to be identified. In this study we aimed to investigate the promoter mutation spectrum, methylation and gene expression pattern of AKT1 and their relationship with breast cancer.
methodsBy using PCR target sequence enrichment and next-generation sequencing technology, we sequenced AKT1 promoter region in pairs of breast tumor and normal tissues from 95 unselected Chinese breast cancer patients. The methylation of the promoter region and the expression profile of AKT1 in the same cohort were detected with bisulfite next-generation sequencing and qPCR, respectively.
resultsWe identified 28 somatic mutations in 23 of the 95 (24.2%) breast cancer samples. And 19 of the 28 mutations were located in transcription factor (TF) binding sites. In the 23 patients with somatic mutations, no significant change of methylation or expression was found comparing with other patients. AKT1 promoter region was significantly hypo-methylated in tumor compared with matched normal tissue (P = 0.0014) in the 95 patients. The expression of AKT1 was significantly suppressed in tumor tissue (P = 0.0375). In clinicopathological factor analysis, AKT1 showed significant hypo-methylation (P = 0.0249) and suppressed expression (P = 0.0375) in HER2 negative subtype. And a trend of decrease in expression level (P = 0.0624) of AKT1 in the ER negative subtype was observed, which is significantly decreased in basal-like breast tumor (P = 0.0328).
conclusionsHypo-methylation and suppressed expression of AKT1 was observed to be associated with breast cancer in our cohort. The methylation and expression of AKT1 were both significantly associated with HER2 status. The promoter mutation of AKT1 did not show significant association with its methylation and expression status. These results suggested that the promoter mutation, methylation and gene expression of AKT1 may play distinct roles in tumorgenesis of breast cancer and the integrated analysis of methylation and expression of AKT1 might serve as potential biomarkers for diagnosis and classification of breast cancer.
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