Gene Summary

Gene:AKT1; AKT serine/threonine kinase 1
Summary:The serine-threonine protein kinase encoded by the AKT1 gene is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components of the apoptotic machinery. Mutations in this gene have been associated with the Proteus syndrome. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2011]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:RAC-alpha serine/threonine-protein kinase
Source:NCBIAccessed: 31 August, 2019


What does this gene/protein do?
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Pathways:What pathways are this gene/protein implicaed in?
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Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 31 August 2019 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 31 August, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (7)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Entity Topic PubMed Papers
Breast CancerAKT1 and Breast Cancer View Publications493
Lung CancerAKT1 and Lung Cancer View Publications319
Skin CancerAKT1 and Skin Cancer View Publications68
Soft Tissue SarcomaAKT1 and Sarcoma View Publications69
Bladder CancerAKT1 and Bladder Cancer View Publications34
Cowden SyndromeOccasional AKT1 mutations in Cowden Syndrome
Orloff et al (2013) reported 2 patients with AKT1 mutations out of a series of 91 Cowden Syndrome patients without PTEN mutations. PTEN antagonizes the AKT1/PI3K signaling pathway and has roles in cell cycle, migration, cell polarity, and apoptosis.
View Publications34
Cervical CancerAKT1 and Cervical Cancer View Publications28

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: AKT1 (cancer-related)

Vakili Saatloo M, Aghbali AA, Koohsoltani M, Yari Khosroushahi A
Akt1 and Jak1 siRNA based silencing effects on the proliferation and apoptosis in head and neck squamous cell carcinoma.
Gene. 2019; 714:143997 [PubMed] Related Publications
Based on Akt1 and Jak1 key roles in apoptosis and proliferation of many cancers, the aim of this study was to find a new gene therapy strategy by silencing of these main anti-apoptotic genes for HNSCC treatment. Cancerous HN5 and normal HUVEC cell lines were treated with Akt1 and Jak1 siRNAs alone or with each other combined with/without cisplatin. The MTS, flow cytometry, 4',6-diamidino-2-phenylindole staining, real-time PCR and ELISA methods were utilized in this study. The highest percentage of apoptosis was observed in the treatment of Jak1 siRNA/cisplatin group in cancerous HN5 cells (96.5%) where this treatment showed 12.84% apoptosis in normal HUVEC cell line. Cell viability reduced significantly to 64.57% after treatment with Akt1 siRNA in HN5 treated group. Knocking down Akt1 and Jak1 genes using siRNAs could increase levels of apoptosis and reduce proliferation rate in HNSCC indicating the powerful effects of these genes siRNAs with or without chemotherapeutic agents in HNSCC treatment. In conclusion, the combination of siRNA-mediated gene-silencing strategy can be considered as a valuable and safe approach for sensitizing cancer cells to chemotherapeutic agents thus proposed further studies regarding this issue to approve some siRNA based therapeutics for using in clinic.

Yoo SK, Song YS, Lee EK, et al.
Integrative analysis of genomic and transcriptomic characteristics associated with progression of aggressive thyroid cancer.
Nat Commun. 2019; 10(1):2764 [PubMed] Free Access to Full Article Related Publications
Anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) show fatal outcomes, unlike DTCs. Here, we demonstrate mutational landscape of 27 ATCs and 86 advanced DTCs by massively-parallel DNA sequencing, and transcriptome of 13 ATCs and 12 advanced DTCs were profiled by RNA sequencing. TERT, AKT1, PIK3CA, and EIF1AX were frequently co-mutated with driver genes (BRAF

Yang Q, Wang R, Wei B, et al.
Gene and microRNA Signatures Are Associated with the Development and Survival of Glioblastoma Patients.
DNA Cell Biol. 2019; 38(7):688-699 [PubMed] Related Publications
This study was aimed to identify hub genes associated with the development of glioblastoma (GBM) by conducting a bioinformatic analysis. The raw gene expression data were downloaded from the Gene Expression Omnibus database and The Cancer Genome Atlas project. After the differentially expressed genes (DEGs) were identified, the functional enrichment analysis of DEGs was conducted. Subsequently, the protein-protein interaction (PPI) network, molecular complex detection clusters, and transcriptional factor (TF)-miRNA-target regulatory network were constructed, respectively. Furthermore, the survival analysis of prognostic outcomes and genes was analyzed. In addition, the expression of key genes was validated by quantitative real-time PCR (qRT-PCR) analysis. A total of 884 DEGs, including 418 upregulated and downregulated genes, were identified between GBM and normal samples. The PPI network comprised a set of 3418 pairs involving 751 nodes, and

Liu Q, Wu Q, Yu M, et al.
Emerging relationships between papillary proliferation of the endometrium and endometrial carcinoma: evidence from an immunohistochemical and molecular analysis.
Virchows Arch. 2019; 475(2):201-209 [PubMed] Related Publications
Papillary proliferation of the endometrium (PPE) is an uncommon lesion that frequently shows mucinous metaplasia. PPE occasionally has concurrent or preceding endometrial hyperplasia and carcinomas, but there is little molecular evidence to support the relationships between PPEs and endometrial neoplasia. In this study, we analyzed the clinicopathological and immunohistochemical features in 30 PPEs (22 simple PPEs and 8 complex papillary hyperplasia (CPH)). Hotspot mutations of KRAS, PI3KCA, AKT1, PTEN (exons 3, 5, and 7), and ARID1A (exons 1 and 14) were detected by pyrosequencing or bidirectional Sanger sequencing. We found that endometrial hyperplasia and carcinoma were more common in CPHs (4/6, 66.7%) than in simple PPEs (4/21, 19.0%) (p < 0.05). Compared with the adjacent normal endometrium, PPEs frequently showed loss of PAX2 (56.7%) and PTEN (10%) expression, diffuse p16 expression (36.7%), decreased PR expression (84.3%), and lower Ki67 labeling index (median 1%, range 1-15%). Simple PPEs and CPHs had similar immunohistochemical features (p > 0.05). KRAS mutations were identified in 14 PPEs and 1 concurrent endometrial carcinoma. The prevalence of KRAS mutations was not statistically different between simple PPEs (10/21, 45.5%) and CPHs (4/8, 50%) (p > 0.05), but was higher in PPEs displaying mucinous metaplasia (12/24, 50%) than in those without (2/6, 33.3%) (p < 0.05). One simple PPE with a KRAS mutation had an AKT1 mutation. No PPEs demonstrated mutations in PI3KCA, PTEN, and ARID1A. In conclusion, both simple PPE and CPH share some common molecular alterations with endometrial neoplasia, in which, KRAS mutations might be a driver.

Hung KC, Wang SG, Lin ML, Chen SS
Citrate-Induced p85α⁻PTEN Complex Formation Causes G
Int J Mol Sci. 2019; 20(9) [PubMed] Free Access to Full Article Related Publications
Citrate is a key intermediate of the tricarboxylic acid cycle and acts as an allosteric signal to regulate the production of cellular ATP. An elevated cytosolic citrate concentration inhibits growth in several types of human cancer cells; however, the underlying mechanism by which citrate induces the growth arrest of cancer cells remains unclear. The results of this study showed that treatment of human pharyngeal squamous carcinoma (PSC) cells with a growth-suppressive concentration of citrate caused cell cycle arrest at the G

Jin H, Jang Y, Cheng N, et al.
Restoration of mutant K-Ras repressed miR-199b inhibits K-Ras mutant non-small cell lung cancer progression.
J Exp Clin Cancer Res. 2019; 38(1):165 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: miRNAs play crucial role in the progression of K-Ras-mutated nonsmall cell lung cancer (NSCLC). However, most studies have focused on miRNAs that target K-Ras. Here, we investigated miRNAs regulated by mutant K-Ras and their functions.
METHODS: miRNAs regulated by mutant K-Ras were screened using miRNA arrays. miR-199b expression levels were measured by qRT-PCR. The protein expression levels were measured using Western blot and immunohistochemistry. The effects of miR-199b on NSCLC were examined both in vitro and in vivo by overexpressing or inhibiting miR-199b. DNA methylation was measured by bisulfite sequencing.
RESULTS: An inverse correlation was observed between K-Ras mutation status and miR-199b levels in NSCLC specimens and cell lines. The inhibition of miR-199b stimulated NSCLC growth and metastasis, while restoration of miR-199b suppressed K-Ras mutation-driven lung tumorigenesis as well as K-Ras-mutated NSCLC growth and metastasis. miR-199b inactivated ERK and Akt pathways by targeting K-Ras, KSR2, PIK3R1, Akt1, and Rheb1. Furthermore, we determined that mutant K-Ras inhibits miR-199b expression by increasing miR-199b promoter methylation.
CONCLUSION: Our findings suggest that mutant K-Ras plays an oncogenic role through downregulating miR-199b in NSCLC and that overexpression of miR-199b is a novel strategy for the treatment of K-Ras-mutated NSCLC.

Sur S, Nakanishi H, Steele R, Ray RB
Depletion of PCAT-1 in head and neck cancer cells inhibits tumor growth and induces apoptosis by modulating c-Myc-AKT1-p38 MAPK signalling pathways.
BMC Cancer. 2019; 19(1):354 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) represents one of the most common malignancies worldwide with a high mortality rate mainly due to lack of early detection markers, frequent association with metastasis and aggressive phenotype. Recently, long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancers. The lncRNA prostate cancer-associated transcript 1 (PCAT-1) showed potential oncogenic roles in different cancers, however its role in HNSCC is not known. In this study, we evaluated the role of the PCAT-1 in HNSCC.
METHODS: The expression of PCAT-1 was measured by quantitative real-time PCR in 23 paired human HNSCC tissues and adjacent non-tumor tissue specimens. Cell proliferation after depleting PCAT-1 was determined. Effect of PCAT-1 depletion in HNSCC cell lines was determined by qRT-PCR and Western blot analyses. Finally, JHU029 HNSCC cells was implanted subcutaneously into athymic nude mice and therapeutic potential of PCAT-1 was investigated.
RESULTS: Up-regulation of PCAT-1 in TCGA dataset of HNSCC was noted. We also observed increased expression of PCAT-1 in archived HNSCC patient samples as compared to adjacent non-tumor tissues. Knockdown of PCAT-1 significantly reduced cell proliferation in HNSCC cell lines. Mechanistic study revealed significant down regulation of c-Myc and AKT1 gene in both RNA and protein levels upon knockdown of PCAT-1. We observed that c-Myc and AKT1 positively correlate with PCAT-1 expression in HNSCC. Further, we observed activation of p38 MAPK and apoptosis signal-regulating kinase 1 upon knockdown of PCAT-1 which induces Caspase 9 and PARP mediated apoptosis. Targeted inhibition of PCAT-1 regresses tumor growth in nude mice.
CONCLUSION: Together our data demonstrated an important role of the PCAT-1 in HNSCC and might serve as a target for HNSCC therapy.

Ma Q, Lu Y, Gu Y
ENKUR Is Involved in the Regulation of Cellular Biology in Colorectal Cancer Cells via PI3K/Akt Signaling Pathway.
Technol Cancer Res Treat. 2019; 18:1533033819841433 [PubMed] Free Access to Full Article Related Publications
Colorectal cancer is one of the most prevalent malignancies worldwide. ENKUR is a transient receptor potential canonical-binding protein that acts as a potential regulator or effector of transient receptor potential canonical channels. It also directly interacts with the p85 regulatory subunit of phosphoinositide 3-kinase. However, the role of ENKUR in colorectal cancer remains unclear. In the present study, the expression profiles of ENKUR in the The Cancer Genome Atlas and ONCOMINE databases were analyzed. Significant downregulation of ENKUR was observed in clinical tumor samples of various cancer types, including colorectal cancer. Decreased ENKUR messenger RNA expression and ENKUR protein level were detected in 6 human colorectal cancer cell lines. Silencing of ENKUR in colorectal cancer cells led to enhanced cell proliferation, migration, and invasion, while the opposite effects were achieved in ENKUR-overexpressing cells. Furthermore, ENKUR-underexpressing cells exhibited increased activity of phosphoinositide 3-kinase /Akt signaling pathway. Downregulation of the epithelial marker, E-cadherin, and upregulation of the mesenchymal markers, vimentin and N-cadherin, were detected in ENKUR-underexpressing cells, suggesting the induction of epithelial-mesenchymal transition. In conclusion, the present study demonstrates that ENKUR may be responsible for alterations in the proliferative, migratory, and invasive potential of colorectal cancer cells through possible involvement in the phosphoinositide 3-kinase /Akt signaling pathway.

Fan X, Wu X
MicroRNA-122-5p promotes the development of non-small cell lung cancer via downregulating p53 and activating PI3K-AKT pathway.
J BUON. 2019 Jan-Feb; 24(1):273-279 [PubMed] Related Publications
PURPOSE: To investigate the role of microRNA-122-5p in the pathogenesis of non-small cell lung cancer (NSCLC) and its underlying mechanism.
METHODS: A total of 72 pairs of NSCLC tissues and paracancerous tissues were collected. The expression level of microRNA-122-5p in NSCLC tissues and paracancerous tissues were detected by qRT-PCR (quantitative real-time polymerase chain reaction). The relationship between microRNA-122-5p expression and the clinical prognosis of NSCLC patients was then analyzed. Bioinformatics prediction and luciferase activity assay were performed to validate the direct binding of microRNA-122-5p and p53. Cell cycle, proliferation, and apoptosis were detected after microRNA-122-5p knockdown in NSCLC cells. The regulatory effect of microRNA-122-5p on promoting NSCLC development was detected by Western blot.
RESULTS: MicroRNA-122-5p was more overexpressed in NSCLC tissues than in paracancerous tissues. MicroRNA-122-5p expression was negatively correlated with survival rate of NSCLC patients. Besides, microRNA-122-5p knockdown remarkably inhibited the proliferation and cell cycle advancement and increased apoptosis of NSCLC cells. Luciferase reporter gene assay and Western blot results indicated that microRNA-122-5p downregulated p53 and activated PI3K-AKT pathway, thereby promoting NSCLC development.
CONCLUSION: MicroRNA-122-5p is overexpressed in NSCLC. Overexpression of microRNA-122-5p promotes NSCLC development by downregulating p53 and activating PI3K-AKT pathway.

Yang F, Xu J, Li H, et al.
FBXW2 suppresses migration and invasion of lung cancer cells via promoting β-catenin ubiquitylation and degradation.
Nat Commun. 2019; 10(1):1382 [PubMed] Free Access to Full Article Related Publications
FBXW2 inhibits proliferation of lung cancer cells by targeting SKP2 for degradation. Whether and how FBXW2 regulates tumor invasion and metastasis is previously unknown. Here, we report that FBXW2 is an E3 ligase for β-catenin. FBXW2 binds to β-catenin upon EGF-AKT1-mediated phosphorylation on Ser

Afshar E, Hashemi-Arabi M, Salami S, et al.
Screening of acetaminophen-induced alterations in epithelial-to-mesenchymal transition-related expression of microRNAs in a model of stem-like triple-negative breast cancer cells: The possible functional impacts.
Gene. 2019; 702:46-55 [PubMed] Related Publications
Current protocols for therapy inefficiently targets triple negative breast cancer and barely eradicate cancer stem cells. Elucidation of the pleiotropic effect of clinically proven therapeutics on cancer cells shed light on novel application of old friends. The pleiotropic effect of acetaminophen (APAP) on breast cancer was previously reported. In a cell model of triple negative breast cancer with stem-like CD44

Harada K, Okamoto W, Mimaki S, et al.
Comparative sequence analysis of patient-matched primary colorectal cancer, metastatic, and recurrent metastatic tumors after adjuvant FOLFOX chemotherapy.
BMC Cancer. 2019; 19(1):255 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: In the era of genome-guided personalized cancer treatment, we must understand chemotherapy-induced genomic changes in tumors. This study evaluated whether adjuvant FOLFOX chemotherapy modifies the mutational profile of recurrent colorectal cancer (CRC).
METHODS: Whole exome sequencing was performed on samples from primary CRC tumors, untreated metastatic tumors, and recurrent tumors following adjuvant FOLFOX chemotherapy. The samples were resected from four patients.
RESULTS: The number of mutations or the mutation spectrum in individual patients was nearly identical. Copy number variants persisted regardless of FOLFOX therapy administration. The genomic signature of oxaliplatin exposure (G > T/C > A, T > A/A > T) was not enriched after FOLFOX chemotherapy. Overlapping single nucleotide variants (SNVs) and indels remained in 26-65% of the patient-matched tumor samples. One patient harbored an AKT1 E17K mutation in the recurrent tumor, whereas PIK3CA E542K and E88Q mutations were detected in the primary and untreated metastatic tumor samples. Genes related to intracellular Ca
CONCLUSIONS: We found that the mutation rates, mutation spectrum, and copy number variants were nearly identical regardless of the administration of FOLFOX therapy in the four CRC cases. The mutational discordance between the patient-matched tumor samples is likely caused by tumor heterogeneity and chemotherapy-induced clonal selection. These findings might be useful as pilot data for larger studies to clarify the changes in the mutational landscape induced by adjuvant FOLFOX chemotherapy.

Jiang M, Chen Y, Deng L, et al.
Upregulation of
DNA Cell Biol. 2019; 38(5):476-484 [PubMed] Related Publications
Recently, sperm-associated antigen 6 (

Cappellesso R, Lo Mele M, Munari G, et al.
Molecular characterization of "sessile serrated" adenoma to carcinoma transition in six early colorectal cancers.
Pathol Res Pract. 2019; 215(5):957-962 [PubMed] Related Publications
Colorectal cancer (CRC) is a heterogeneous group of diseases both from the morphological and molecular point of view. The sessile serrated adenoma/polyp (SSA/P) has been proposed as the precursor lesion of CRCs characterized by CpG island methylator phenotype (CIMP), DNA mismatch repair (MMR) system deficiency, and BRAF gene mutations. However, no study so far investigated the molecular landscape of "sessile serrated" adenoma to carcinoma transition in early CRCs. Six formalin-fixed paraffin-embedded CRCs developed within SSA/P were profiled for the immunohistochemical expression of MMR proteins (MLH1, MSH2, MSH6, PMS2, and Ep-CAM), p16, and β-catenin. DNA was extracted from the two components of each sample, after microdissection, and characterized for CIMP status and by applying a custom hotspot multigene mutational profiling of 164 hotspot regions of eleven CRC-associated genes (AKT1, APC, BRAF, CTNNB1, KIT, KRAS, NRAS, PDGFRA, PIK3CA, PTEN, and TP53). Five out of the six CRCs shared the same molecular profile (i.e. CIMP positive, MSI status, and BRAF mutation) with their SSA/P components. One out of five CRCs was also APC mutated, whereas another one showed an additional TP53 mutation. The remaining case was CIMP negative and MMR proficient in both the components, harbored a BRAF mutation in the SSA/P counterpart, whereas the CRC one was APC and TP53 mutated and showed p16 and β-catenin dysregulation. This study provides the molecular evidence that SSA/P, even without cytological dysplasia, is a precursor lesion of CRC and that conventional CRC might arise from mixed polyp.

Zhang X, Wang S, Wang H, et al.
Circular RNA circNRIP1 acts as a microRNA-149-5p sponge to promote gastric cancer progression via the AKT1/mTOR pathway.
Mol Cancer. 2019; 18(1):20 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: CircRNA has emerged as a new non-coding RNA that plays crucial roles in tumour initiation and development. 'MiRNA sponge' is the most reported role played by circRNAs in many tumours. The AKT/mTOR axis is a classic signalling pathway in cancers that sustains energy homeostasis through energy production activities, such as the Warburg effect, and blocks catabolic activities, such as autophagy. Additionally, the AKT/mTOR axis exerts a positive effect on EMT, which promotes tumour metastasis.
METHODS: We detected higher circNRIP1 expression in gastric cancer by performing RNA-seq analysis. We verified the tumour promotor role of circNRIP1 in gastric cancer cells through a series of biological function assays. We then used a pull-down assay and dual-luciferase reporter assay to identify the downstream miR-149-5p of circNRIP1. Western blot analysis and immunofluorescence assays were performed to demonstrate that the circNRIP1-miR-149-5p-AKT1/mTOR axis is responsible for the altered metabolism in GC cells and promotes GC development. We then adopted a co-culture system to trace circNRIP1 transmission via exosomal communication and RIP experiments to determine that quaking regulates circNRIP1 expression. Finally, we confirmed the tumour suppressor role of microRNA-133a-3p in vivo in PDX mouse models.
RESULTS: We discovered that knockdown of circNRIP1 successfully blocked proliferation, migration, invasion and the expression level of AKT1 in GC cells. MiR-149-5p inhibition phenocopied the overexpression of circNRIP1 in GC cells, and overexpression of miR-149-5p blocked the malignant behaviours of circNRIP1. Moreover, it was proven that circNRIP1 can be transmitted by exosomal communication between GC cells, and exosomal circNRIP1 promoted tumour metastasis in vivo. We also demonstrated that quaking can promote circNRIP1 transcription. In the final step, the tumour promotor role of circNRIP1 was verified in PDX models.
CONCLUSIONS: We proved that circNRIP1 sponges miR-149-5p to affect the expression level of AKT1 and eventually acts as a tumour promotor in GC.

Guo J, Dai X, Laurent B, et al.
AKT methylation by SETDB1 promotes AKT kinase activity and oncogenic functions.
Nat Cell Biol. 2019; 21(2):226-237 [PubMed] Free Access to Full Article Related Publications
Aberrant activation of AKT disturbs the proliferation, survival and metabolic homeostasis of various human cancers. Thus, it is critical to understand the upstream signalling pathways governing AKT activation. Here, we report that AKT undergoes SETDB1-mediated lysine methylation to promote its activation, which is antagonized by the Jumonji-family demethylase KDM4B. Notably, compared with wild-type mice, mice harbouring non-methylated mutant Akt1 not only exhibited reduced body size but were also less prone to carcinogen-induced skin tumours, in part due to reduced AKT activation. Mechanistically, the interaction of phosphatidylinositol (3,4,5)-trisphosphate with AKT facilitates its interaction with SETDB1 for subsequent AKT methylation, which in turn sustains AKT phosphorylation. Pathologically, genetic alterations, including SETDB1 amplification, aberrantly promote AKT methylation to facilitate its activation and oncogenic functions. Thus, AKT methylation is an important step, synergizing with PI3K signalling to control AKT activation. This suggests that targeting SETDB1 signalling could be a potential therapeutic strategy for combatting hyperactive AKT-driven cancers.

Zhan FB, Zhang XW, Feng SL, et al.
MicroRNA-206 Reduces Osteosarcoma Cell Malignancy
Yonsei Med J. 2019; 60(2):163-173 [PubMed] Free Access to Full Article Related Publications
PURPOSE: This study was undertaken to explore how miR-206 represses osteosarcoma (OS) development.
MATERIALS AND METHODS: Expression levels of miR-206, PAX3, and MET mRNA were explored in paired OS and adjacent tissue specimens. A patient-derived OS cell line was established. miR-206 overexpression and knockdown were achieved by lentiviral transduction. PAX3 and MET overexpression were achieved by plasmid transfection. Treatment with hepatocyte growth factor (HGF) was utilized to activate c-Met receptor. Associations between miR-206 and PAX3 or MET mRNA in OS cells were verified by AGO2-RNA immunoprecipitation assay and miRNA pulldown assay. OS cell malignancy was evaluated
RESULTS: Expression levels of miR-206 were significantly decreased in OS tissue specimens, compared to adjacent counterparts, and were inversely correlated with expression of PAX3 and MET mRNA. miR-206 directly interacted with PAX3 and MET mRNA in OS cells. miR-206 overexpression significantly reduced PAX3 and MET gene expression in OS cells
CONCLUSION: miR-206 reduces OS cell malignancy

Li J, Qi Y
Ginsenoside Rg3 inhibits cell growth, migration and invasion in Caco-2 cells by downregulation of lncRNA CCAT1.
Exp Mol Pathol. 2019; 106:131-138 [PubMed] Related Publications
BACKGROUND: Colorectal cancer (CRC) is a troublesome disease with high morbidity and mortality. Ginsenoside Rg3 possesses anti-cancer properties. Colon Cancer Associated Transcript 1 (CCAT1) participates in the genesis, development, invasion and metastasis of colorectal cancer. In our study, we explored the effects of Rg3 on CRC cell line Caco-2 by regulating CCAT1.
METHODS: CRC tissue was obtained from hospital and Caco-2 cells were purchased. Caco-2 cells were treated with Rg3 and/or transfected with pc- CCAT1 or pcDNA3.1. The group without Rg3 treatment was treated as control. Cell viability, cell apoptosis, cell migration and invasion were detected by Cell Counting Kit-8 assay, flow cytometry and Transwell chamber migration/invasion assay, respectively. The expression of CyclinD1, apoptosis related proteins (p53, Bcl-2, Bax, pro-/Cleaved-Caspase-3), migration and invasion related proteins (MMP-9 and vimentin), and phosphatidylinositol 3'-kinase (PI3K)/protein kinase B (AKT) related proteins (p/t-PI3K, p/t-AKT) were examined by western blot. The expression of CCAT1 was measured by quantitative real time RCR (qRT-PCR).
RESULTS: Rg3 significantly decreased cell viability, migration and invasion, and promoted apoptosis. Meanwhile, the expression of Cyclin D1, matrix metalloproteinase (MMP)-9 and vimentin was downregulated. The expression of apoptosis-related proteins p53, Bax, and Cleaved-Caspase-3 were upregulated while Bcl-2 was downregulated by the treatment of Rg3 compared with control. Furthermore, CCAT1 was upregulated in CRC tissue and Rg3 negatively regulated CCAT1 expression. Transfection with pc-CCAT1 led to the opposite results as compared with transfection with pcDNA3.1 in Rg3 treated cells. In addition, Rg3 decreased the phosphorylation of PI3K and AKT.
CONCLUSION: Ginsenoside Rg3 inhibits migration and invasion, and promotes apoptosis of Caco-2 cells by suppression expression of LncRNA CCAT1.

Gao XH, Yu GY, Hong YG, et al.
Clinical significance of multiple gene detection with a 22-gene panel in formalin-fixed paraffin-embedded specimens of 207 colorectal cancer patients.
Int J Clin Oncol. 2019; 24(2):141-152 [PubMed] Related Publications
BACKGROUND: Simultaneous detection of multiple molecular biomarkers is helpful in the prediction of treatment response and prognosis for colorectal cancer (CRC) patients.
METHODS: A 22-gene panel consisting of 103 hotspot regions was utilized in the formalin-fixed paraffin-embedded (FFPE) tissue samples of 207 CRC patients, using the next-generation sequencing (NGS)-based multiplex PCR technique. Those 22 genes included AKT1, ALK, BRAF, CTNNB1, DDR2, EGFR, ERBB2, ERBB4, FBXW7, FGFR1, FGFR2, FGFR3, KRAS, MAP2K1, MET, NOTCH1, NRAS, PIK3CA, PTEN, SMAD4, STK11, and TP53.
RESULTS: Of the 207 patients, 193 had one or more variants, with 170, 20, and 3 having one, two, and three mutated genes, respectively. Of the total 414 variants identified in this study, 384, 25, and 5 were single-nucleotide variants, deletion, and insertion. The top four frequently mutated genes were TP53, KRAS, PIK3CA, and FBXW7. There was high consistency between the results of NGS-PCR technique and routine ARMS-PCR in KRAS and BRAF mutation detection. Univariate and multivariate analyses demonstrated that advanced TNM stage, elevated serum CEA, total variants number ≥ 2, AKT1 and PTEN mutation were independent predictors of shorter DFS; poor differentiation, advanced TNM stage, total variants number ≥ 2, BRAF, CTNNB1 and NRAS mutation were independent predictors of shorter OS.
CONCLUSIONS: It is feasible to detect multiple gene mutations with a 22-gene panel in FFPE CRC specimens. TNM stage and total variants number ≥ 2 were independent predictors of DFS and OS. Detection of multiple gene mutations may provide additional prognostic information to TNM stage in CRC patients.

Li W, Qiu T, Guo L, et al.
NGS-based oncogenic mutations analysis in advanced colorectal cancer patients improves targeted therapy prediction.
Pathol Res Pract. 2019; 215(3):483-489 [PubMed] Related Publications
BACKGROUND: Characterization of genetic alterations has been revealed to be important to predict the outcomes of targeted therapy in cancer. We here aimed to assess the mutation profiling of 526 colorectal cancer (CRC) patients by next-generation sequencing (NGS) to enable a more personalized anti-EGFR treatment.
METHODS: Tumors were analyzed using NGS to determine hotspot mutations in 22 cancer-related genes.
RESULTS: Mutations were observed in 13 genes in 436 of 526 (82.9%) tumors, and the most common mutations occurred in TP53 and KRAS. PIK3CA mutations usually coexisted with KRAS, NRAS or BRAF mutations. A higher frequency of concomitant PIK3CA mutations was observed in tumors with KRAS outside codon 13 mutations, with NRAS codon 61 mutations and with BRAF kinase-activated mutations. Moreover, KRAS, PIK3CA, AKT1 and FBXW7 mutations were statistically associated with some clinicopathological features, including location, age or metastasis of CRC patients. For RAS wild-type patients treated with cetuximab, longer progression-free survival (PFS) was observed in patients identified as wild type in all 22 genes compared with patients with mutations in one or more genes.
CONCLUSIONS: A wild-type result in all 22 cancer-related genes detected by NGS is associated with a better outcome of cetuximab treatment. Determining mutation patterns by NGS may aid to understand the molecular mechanisms of CRC and improve targeted therapy prediction.

Wang Y, Wang L, Sui M
Long non-coding RNA H19 promotes proliferation of Hodgkin's lymphoma via AKT pathway.
J BUON. 2018 Nov-Dec; 23(6):1825-1831 [PubMed] Related Publications
PURPOSE: To explore whether lncRNA (Long non-coding RNA) H19 could promote the development of Hodgkin's lymphoma (HL) by regulating cell proliferation via AKT pathway.
METHODS: H19 expressions in 60 HL tissues, 40 RH (reactive hyperplasia of lymph nodes) tissues, L428, A20 and Ly1 cell lines were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). H19 siRNA and pcDNA-H19 were constructed. Cell viability after altering H19 expression was detected by EdU and cell counting kit-8 (CCK-8) assay. The mRNA level of AKT in HL tissues and RH tissues was detected by qRT-PCR. The relationship between AKT and H19 was further detected by Western blot.
RESULTS: H19 was overexpressed in HL tissues and cell lines compared with those of controls. HL patients with huge lump and in Ann Arbor stage III-IV presented higher expression of H19. Besides, H19 expression was negatively correlated to overall survival (OS) of HL patients. In vitro experiments suggested that H19 downregulation decreased proliferation and viability of HL cells. AKT expression was upregulated in HL tissues compared with RH tissues, and was positively regulated by H19. Western blot results also indicated that H19 overexpression upregulated protein expression of AKT in HL cells.
CONCLUSIONS: Overexpressed lncRNA H19 promotes HL development by stimulating proliferation of HL cells via AKT pathway.

Zhang Z, Liu X, Xu H, et al.
LINC01170 promotes the progression of endometrial carcinoma by activating the AKT pathway.
J BUON. 2018 Nov-Dec; 23(6):1745-1752 [PubMed] Related Publications
PURPOSE: To investigate the function of LINC01170 in the progression of endometrial carcinoma and its underlying mechanism.
METHODS: The expression profiles and prognostic data of endometrial carcinoma were downloaded by GDC (genomic data commons) analysis tools. Differentially expressed long noncoding (lnc)RNAs were analyzed by the edgeR (empirical analysis of digital gene expression data in R) package. LncRNAs that were related to prognosis of endometrial carcinoma were calculated by the survival function. Moreover, the PHEAT map package was introduced to edit heatmaps of differentially expressed lncRNAs. Human endometrial carcinoma cell lines (Ishikawa, ECC and HEC-IA) were cultured. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expressions of lncRNAs and related genes. Cell proliferation was detected by MTT, and cell cycle and apoptosis were detected by flow cytometry. Additionally, Western blot was used to detect protein expressions of relative genes.
RESULTS: Results showed that LINC01170 was a non-coding RNA. LINC01170 was overexpressed in endometrial carcinoma, which was a risk factor for prognosis of this disease. LINC01170 expressions in carcinoma and para-cancerous tissues of 50 patients with endometrial carcinoma were detected by qRT-PCR and found that the expression level of LINC01170 in endometrial carcinoma was remarkably increased than that of para-cancerous tissues. Moreover, the expression level of LINC01170 in advanced endometrial carcinoma was remarkably higher than that of early-stage disease. After interfering with LINC01170, the proliferation of both the Ishikawa and HEC-1A cells were remarkably decreased, and cell cycle was arrested at the G0/G1 phase. Meanwhile, apoptosis results showed a remarkable apoptosis rate after interfering with LINC01170. Western blot results also demonstrated the decreased activity of AKT pathway and phosphorylated expression of AKT protein after LINC01170 knockdown. In addition, expressions of CDK2, CDK4 and Bcl-2 were decreased after LINC01170 knockdown.
CONCLUSIONS: LINC01170 promotes the progression of endometrial carcinoma through stimulating proliferation, cell cycle transition and inhibiting apoptosis of endometrial carcinoma cells via AKT pathway.

Liang Y, Zhang C, Ma MH, Dai DQ
Identification and prediction of novel non-coding and coding RNA-associated competing endogenous RNA networks in colorectal cancer.
World J Gastroenterol. 2018; 24(46):5259-5270 [PubMed] Free Access to Full Article Related Publications
AIM: To identify and predict the competing endogenous RNA (ceRNA) networks in colorectal cancer (CRC) by bioinformatics analysis.
METHODS: In the present study, we obtained CRC tissue and normal tissue gene expression profiles from The Cancer Genome Atlas project. Differentially expressed (DE) genes (DEGs) were identified. Then, upregulated and downregulated miRNA-centered ceRNA networks were constructed by analyzing the DEGs using multiple bioinformatics approaches. DEmRNAs in the ceRNA networks were identified in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using KEGG Orthology Based Annotation System 3.0. The interactions between proteins were analyzed using the STRING database. Kaplan-Meier survival analysis was conducted for DEGs and real time quantitative polymerase chain reaction (RT-qPCR) was also performed to validate the prognosis-associated lncRNAs in CRC cell lines.
RESULTS: Eighty-one DElncRNAs, 20 DEmiRNAs, and 54 DEmRNAs were identified to construct the ceRNA networks of CRC. The KEGG pathway analysis indicated that nine out of top ten pathways were related with cancer and the most significant pathway was "colorectal cancer". Kaplan-Meier survival analysis showed that the overall survival was positively associated with five DEGs (IGF2-AS, POU6F2-AS2, hsa-miR-32, hsa-miR-141, and SERPINE1) and it was negatively related to three DEGs (LINC00488, hsa-miR-375, and PHLPP2). Based on the STRING protein database, it was found that SERPINE1 and PHLPP2 interact with AKT1. Besides, SERPINE1 can interact with VEGFA, VTN, TGFB1, PLAU, PLAUR, PLG, and PLAT. PHLPP2 can interact with AKT2 and AKT3. RT-qPCR revealed that the expression of IGF2-AS, POU6F2-AS2, and LINC00488 in CRC cell lines was consistent with the
CONCLUSION: CeRNA networks play an important role in CRC. Multiple DEGs are related with clinical prognosis, suggesting that they may be potential targets in tumor diagnosis and treatment.

Tarokhian H, Rahimi H, Mosavat A, et al.
HTLV-1-host interactions on the development of adult T cell leukemia/lymphoma: virus and host gene expressions.
BMC Cancer. 2018; 18(1):1287 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a lymphoproliferative disorder of HTLV-1-host interactions in infected TCD4+ cells. In this study, the HTLV-1 proviral load (PVL) and HBZ as viral elements and AKT1, BAD, FOXP3, RORγt and IFNλ3 as the host factors were investigated.
METHODS: The study was conducted in ATLLs, HTLV-1-associated myelopathy/tropical spastic paraparesis patients (HAM/TSPs) and HTLV-1-asympthomatic carriers (ACs). The DNA and mRNA from peripheral blood mononuclear cells were extracted for gene expression assessments via qRT-PCR, TaqMan assay, and then confirmed by western blotting.
RESULTS: As it was expected, the HTLV-1-PVL were higher in ATLLs than ACs (P = 0.002) and HAM/TSP (P = 0.041). The HBZ expression in ATLL (101.76 ± 61.3) was radically higher than in ACs (0.12 ± 0.05) and HAM/TSP (0.01 ± 0.1) (P = 0.001). Furthermore, the AKT1 expression in ATLLs (13.52 ± 4.78) was higher than ACs (1.17 ± 0.27) (P = 0.05) and HAM/TSPs (0.72 ± 0.49) (P = 0.008). However, BAD expression in ATLL was slightly higher than ACs and HAM/TSPs and not significant. The FOXP3 in ATLLs (41.02 ± 24.2) was more than ACs (1.44 ± 1) (P = 0.007) and HAM/TSP (0.45 ± 0.15) (P = 0.01). However, RORγt in ATLLs (27.43 ± 14.8) was higher than ACs (1.05 ± 0.32) (P = 0.02) but not HAM/TSPs. Finally, the IFNλ3 expression between ATLLs (31.92 ± 26.02) and ACs (1.46 ± 0.63) (P = 0.01) and ACs and HAM/TSPs (680.62 ± 674.6) (P = 0.02) were statistically different, but not between ATLLs and HAM/TSPs.
CONCLUSIONS: The present and our previous study demonstrated that HTLV-1-PVL and HBZ and host AKT1 and Rad 51 are novel candidates for molecular targeting therapy of ATLL. However, high level of RORγt may inhibit Th1 response and complicated in ATLL progressions.

Li Z, Yao JN, Huang WT, et al.
Expression of miR‑542‑3p in osteosarcoma with miRNA microarray data, and its potential signaling pathways.
Mol Med Rep. 2019; 19(2):974-983 [PubMed] Free Access to Full Article Related Publications
Osteosarcoma (OS) is the most common pediatric primary bone tumor, with high malignancy rates and a poor prognosis following metastasis. At present, the role of microRNA (miR)‑542‑3p in OS remains to be elucidated. The purpose of the present study was to investigate the expression level of miR‑542‑3p in OS, and its potential molecular mechanisms, via a bioinformatics analysis. First, the expression of miR‑542‑3p in OS based on the continuous variables of the Gene Expression Omnibus database and PubMed was studied. Subsequently, the potential target genes of miR‑542‑3p were predicted using gene expression profiles and bioinformatics software. On the basis of the Database for Annotation, Visualization and Integrated Discovery, version 6.8, a study of gene ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway knowledge base was conducted to explore the biological value of miR‑542‑3p in OS. Finally, the protein‑protein interaction (PPI) network was completed using the STRING database. The expression of miR‑542‑3p in OS was revealed to be significantly higher compared with that in normal tissue. In total, 1,036 target genes of miR‑542‑3p were obtained. The results of the GO enrichment analysis revealed that the significant terms were 'bone development', 'cell cycle arrest' and 'intracellular signal transduction'. The results of the KEGG analysis revealed the highlighted pathways that were targeted to miR‑542‑3p, including the sphingolipid signaling pathway (P=3.91x10‑5), the phosphoinositide 3‑kinase (PI3K)‑AKT serine/threonine kinase (AKT) signaling pathway (P=3.17x10‑5) and the insulin signaling pathway (P=1.04x10‑5). The PPI network revealed eight hub genes: Ubiquitin‑60S ribosomal protein L40, Ras‑related C3 botulinum toxin substrate, mitogen‑activated protein kinase 1, epidermal growth factor receptor, cystic fibrosis transmembrane conductance regulator, PI3K regulatory subunit 1, AKT1, and actin‑related protein 2/3 complex subunit 1A, which may be the key target genes of miR‑542‑3p in OS. Taken together, these results have demonstrated that miR‑542‑3p was overexpressed in OS. The potential target genes and biological functions of miR‑542‑3p may provide novel insights into the differentially expressed genes that are involved in OS.

Gillison ML, Akagi K, Xiao W, et al.
Human papillomavirus and the landscape of secondary genetic alterations in oral cancers.
Genome Res. 2019; 29(1):1-17 [PubMed] Free Access to Full Article Related Publications
Human papillomavirus (HPV) is a necessary but insufficient cause of a subset of oral squamous cell carcinomas (OSCCs) that is increasing markedly in frequency. To identify contributory, secondary genetic alterations in these cancers, we used comprehensive genomics methods to compare 149 HPV-positive and 335 HPV-negative OSCC tumor/normal pairs. Different behavioral risk factors underlying the two OSCC types were reflected in distinctive genomic mutational signatures. In HPV-positive OSCCs, the signatures of APOBEC cytosine deaminase editing, associated with anti-viral immunity, were strongly linked to overall mutational burden. In contrast, in HPV-negative OSCCs, T>C substitutions in the sequence context 5'-ATN-3' correlated with tobacco exposure. Universal expression of HPV

Urtishak KA, Wang LS, Culjkovic-Kraljacic B, et al.
Targeting EIF4E signaling with ribavirin in infant acute lymphoblastic leukemia.
Oncogene. 2019; 38(13):2241-2262 [PubMed] Free Access to Full Article Related Publications
The poor outcomes in infant acute lymphoblastic leukemia (ALL) necessitate new treatments. Here we discover that EIF4E protein is elevated in most cases of infant ALL and test EIF4E targeting by the repurposed antiviral agent ribavirin, which has anticancer properties through EIF4E inhibition, as a potential treatment. We find that ribavirin treatment of actively dividing infant ALL cells on bone marrow stromal cells (BMSCs) at clinically achievable concentrations causes robust proliferation inhibition in proportion with EIF4E expression. Further, we find that ribavirin treatment of KMT2A-rearranged (KMT2A-R) infant ALL cells and the KMT2A-AFF1 cell line RS4:11 inhibits EIF4E, leading to decreases in oncogenic EIF4E-regulated cell growth and survival proteins. In ribavirin-sensitive KMT2A-R infant ALL cells and RS4:11 cells, EIF4E-regulated proteins with reduced levels of expression following ribavirin treatment include MYC, MCL1, NBN, BCL2 and BIRC5. Ribavirin-treated RS4:11 cells exhibit impaired EIF4E-dependent nuclear to cytoplasmic export and/or translation of the corresponding mRNAs, as well as reduced phosphorylation of the p-AKT1, p-EIF4EBP1, p-RPS6 and p-EIF4E signaling proteins. This leads to an S-phase cell cycle arrest in RS4:11 cells corresponding to the decreased proliferation. Ribavirin causes nuclear EIF4E to re-localize to the cytoplasm in KMT2A-AFF1 infant ALL and RS4:11 cells, providing further evidence for EIF4E inhibition. Ribavirin slows increases in peripheral blasts in KMT2A-R infant ALL xenograft-bearing mice. Ribavirin cooperates with chemotherapy, particularly L-asparaginase, in reducing live KMT2A-AFF1 infant ALL cells in BMSC co-cultures. This work establishes that EIF4E is broadly elevated across infant ALL and that clinically relevant ribavirin exposures have preclinical activity and effectively inhibit EIF4E in KMT2A-R cases, suggesting promise in EIF4E targeting using ribavirin as a means of treatment.

Lin MW, Su KY, Su TJ, et al.
Clinicopathological and genomic comparisons between different histologic components in combined small cell lung cancer and non-small cell lung cancer.
Lung Cancer. 2018; 125:282-290 [PubMed] Related Publications
OBJECTIVE: Histologic transformation from adenocarcinoma to small cell lung cancer (SCLC) is one of the mechanisms of acquired resistance after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. Furthermore, de novo combined SCLC/non-small cell lung cancer (NSCLC) have occasionally been reported; however, their mutational statuses and clinicopathological features have not yet been elucidated. In this study, we aimed to profile the genetic backgrounds of these 2 different histologic components by investigating patients with de novo combined SCLC/NSCLC as well as those with lung adenocarcinoma who experienced SCLC transformation after TKI treatment.
MATERIALS AND METHODS: Four patients with de novo combined SCLC/NSCLC were investigated, as were 4 other patients with lung adenocarcinoma who experienced SCLC transformation after TKI treatment. The different histologic components of the tumors in each patient were tested for thyroid transcription factor-1, p40, synaptophysin, chromogranin A, p53, retinoblastoma protein (Rb), and achaete-scute homolog 1 (ASCL1) via immunohistochemistry, and were macroscopically dissected for mutational analysis using next-generation sequencing with the Oncomine Focus Assay and Comprehensive Assay panel.
RESULTS: The distinct histologic components in patients with de novo combined SCLC/NSCLC and those with adenocarcinoma exhibiting small cell transformation showed high consistency in EGFR/TP53/RB1 mutations, and expression patterns of p53 and Rb. A high frequency of activating mutations involving PI3K/AKT1 signaling pathway was observed in SCLC. Nuclear ASCL1 expression was present in SCLC but absent or barely present in adenocarcinoma in 7 cases.
CONCLUSIONS: Our data imply that inactivation of TP53/RB1 function is a possible early event in the histogenesis of synchronous and metachronous SCLC/NSCLC. Moreover, the non-adenocarcinoma (SCLC) component might arise from the adenocarcinoma (NSCLC) component through a mechanism that involves the activation of the ASCL1 and PI3K/AKT1 signaling pathways.

Wei CY, Zhu MX, Lu NH, et al.
Bioinformatics-based analysis reveals elevated MFSD12 as a key promoter of cell proliferation and a potential therapeutic target in melanoma.
Oncogene. 2019; 38(11):1876-1891 [PubMed] Free Access to Full Article Related Publications
Although recent therapeutic advances based on our understanding of molecular phenomena have prolonged the survival of melanoma patients, the prognosis of melanoma remains dismal and further understanding of the underlying mechanism of melanoma progression is needed. In this study, differential expression analyses revealed that many genes, including AKT1 and CDK2, play important roles in melanoma. Functional analyses of differentially expressed genes (DEGs), obtained from the GEO (Gene Expression Omnibus) database, indicated that high proliferative and metastatic abilities are the main characteristics of melanoma and that the PI3K and MAPK pathways play essential roles in melanoma progression. Among these DEGs, major facilitator superfamily domain-containing 12 (MFSD12) was found to have significantly and specifically upregulated expression in melanoma, and elevated MFSD12 level promoted cell proliferation by promoting cell cycle progression. Mechanistically, MFSD12 upregulation was found to activate PI3K signaling, and a PI3K inhibitor reversed the increase in cell proliferation endowed by MFSD12 upregulation. Clinically, high MFSD12 expression was positively associated with shorter overall survival (OS) and disease-free survival (DFS) in melanoma patients, and MFSD12 was an independent prognostic factor for OS and DFS in melanoma patients. Therapeutically, in vivo assays further confirmed that MFSD12 interference inhibited tumor growth and lung metastasis in melanoma. In conclusion, elevated MFSD12 expression promotes melanoma cell proliferation, and MFSD12 is a valuable prognostic biomarker and promising therapeutic target in melanoma.

Venur VA, Santagata S, Galanis E, Brastianos PK
New molecular targets in meningiomas: the present and the future.
Curr Opin Neurol. 2018; 31(6):740-746 [PubMed] Related Publications
PURPOSE OF REVIEW: Meningiomas, the most common primary brain tumor, have historically been managed with surgery and radiation. Traditional chemotherapy has not been effective. Fortunately, recent advances in genetic sequencing have led to an improved understanding of the molecular drivers in meningioma. This article aims to discuss the diagnostic and therapeutic implications of recently discovered genetic alterations in meningiomas.
RECENT FINDINGS: Many of the recently discovered genetic alterations correlate with distinct clinical phenotypes. SMO, AKT and PIK3CA mutations are enriched in the anterior skull base. KLF4 mutations are specific for secretory histology, and BAP1 alterations are common in progressive rhabdoid meningiomas. Alterations in TERT, DMD and BAP1 correlate with poor clinical outcomes. Importantly, the discovery of clinically actionable alterations in a number of genes, including SMO, AKT1 and PIK3CA, has opened up novel potential avenues for therapeutic management of meningiomas. Overexpression of PD-L1 in higher grade meningiomas also provides preclinical support for the investigation of checkpoint blockade.
SUMMARY: The discovery of genetic alterations has improved our understanding of the natural history and classification of meningiomas. Clinical trials with several novel agents targeting driver mutations are currently accruing patients and they can lead to better treatment strategies.

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Cite this page: Cotterill SJ. v-akt murine thymoma viral oncogene homolog 1 (14q32.3), Cancer Genetics Web: http://www.cancer-genetics.org/AKT1.htm Accessed:

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