GATA3 and APOBEC3B are prognostic markers in adrenocortical carcinoma and APOBEC3B is directly transcriptionally regulated by GATA3

Gara, Sudheer Kumar; Tyagi, Monica; Patel, Dhaval; Gaskins, Kelli; Lack, Justin; Liu, Yi; Kebebew, Electron

doi:10.18632/oncotarget.27703

Cited by 9 publications

(7 citation statements)

References 44 publications

(58 reference statements)

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“…Thus, in the case of multiple myeloma, a high level of APOBECmediated transitions gives an unfavorable prognosis [113,114]. A similar observation was made for APO-BEC3B in cohorts of patients with adrenal carcinoma selected from the Cancer Genome Atlas database [115] and patients with ovarian cancer [116].…”

Section: Mechanisms Of Aid/apobec Expression Impairment In Tumorssupporting

confidence: 56%

Mutagenic Activity of AID/APOBEC Deaminases in Antiviral Defense and Carcinogenesis

2022

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Proteins of the AID/APOBEC family are capable of cytidine deamination in nucleic acids forming uracil. These enzymes are involved in mRNA editing, protection against viruses, the introduction of point mutations into DNA during somatic hypermutation, and antibody isotype switching. Since these deaminases, especially AID, are potent mutagens, their expression, activity, and specificity are regulated by several intracellular mechanisms. In this review, we discuss the mechanisms of impaired expression and activation of AID/APOBEC proteins in human tumors and their role in carcinogenesis and tumor progression. Also, the diagnostic and potential therapeutic value of increased expression of AID/APOBEC in different types of tumors is analyzed. We assume that in the case of solid tumors, increased expression of endogenous deaminases can serve as a marker of response to immunotherapy since multiple point mutations in host DNA could lead to amino acid substitutions in tumor proteins and thereby increase the frequency of neoepitopes.

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Section: Mechanisms Of Aid/apobec Expression Impairment In Tumorssupporting

confidence: 56%

Mutagenic Activity of AID/APOBEC Deaminases in Antiviral Defense and Carcinogenesis

2022

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“…A similar result was also found for adrenocortical adenocarcinoma (ACC) patients expressing GATA3, GATA2, and SOX11 (Additional file 4: Fig. S3) [54].…”

Section: Timer2 Analysis Shows An Association Of the 38 Tfs With Patient Survival Across Cancer Typessupporting

confidence: 80%

Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors

et al. 2021

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Aim Neuroblastoma is a heterogeneous childhood cancer derived from the neural crest. The dual cell identities of neuroblastoma include Mesenchymal (MES) and Adrenergic (ADRN). These identities are conferred by a small set of tightly-regulated transcription factors (TFs) binding super enhancers, collectively forming core regulatory circuitries (CRCs). The purpose of this study was to gain a deep understanding of the role of MES and ADRN TFs in neuroblastoma and other cancers as potential indicators of disease prognosis, progression, and relapse. Methods To that end, we first investigated the expression and mutational profile of MES and ADRN TFs in neuroblastoma. Moreover, we established their correlation with neuroblastoma risk groups and overall survival while establishing their extended networks with long non-coding RNAs (lncRNAs). Furthermore, we analysed the pan-cancer expression and mutational profile of these TFs and their correlation with patient survival and finally their network connectivity, using a panel of bioinformatic tools including GEPIA2, human pathology atlas, TIMER2, Omicsnet, and Cytoscape. Results We show the association of multiple MES and ADRN TFs with neuroblastoma risk groups and overall survival and find significantly higher expression of various MES and ADRN TFs compared to normal tissues and their association with overall survival and disease-free survival in multiple cancers. Moreover, we report the strong correlation of the expression of these TFs with the infiltration of stromal and immune cells in the tumour microenvironment and with stemness and metastasis-related genes. Furthermore, we reveal extended pan-cancer networks comprising these TFs that influence the tumour microenvironment and metastasis and may be useful indicators of cancer prognosis and patient survival. Conclusion Our meta-analysis shows the significance of MES and ADRN TFs as indicators of patient prognosis and the putative utility of these TFs as potential novel biomarkers.

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“…Recent research has also shown that the expression levels of A3B have a strong positive correlation with tumor mutation loads (11), along with a strong A3B upregulation in the majority of tumor types, including breast, uterus, bladder, head and neck, and lung (adeno-and squamous cell carcinomas) (12), suggesting that A3B may be a general endogenous mutagen that contributes to human cancers. Patients with a higher level of A3B gene expression in their tumors had a lower survival rate as compared to patients with lower expression A3B gene expression in their tumors (13)(14)(15).…”

Section: Introductionmentioning

confidence: 93%

APOBEC3B deletion polymorphism and lung cancer risk in the southern Chinese population

Ben¹,

Tian²,

Liang³

et al. 2021

Ann Transl Med

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Background: Approximately 80-85% of lung cancer is the non-small cell lung cancer (NSCLC) subtype, which ranks as the leading cause of cancer deaths worldwide. APOBEC3B (A3B) was reported to be a key source of mutations in NSCLC. However, the role of the A3B deletion polymorphism in the etiology of NSCLC has not been well-documented.Methods: A case-control study with 317 NSCLC patients and 334 healthy controls was conducted to explore the association between the A3B deletion polymorphism and the risk of NSCLC. The unconditional logistic regression model was performed to calculate the odds ratio (OR) and the 95% confidence interval (CI), and the confounding factors were adjusted, including age, gender, and smoking status, to estimate the risk. An analysis of gene-environment interactions was performed using multifactor dimensionality reduction (MDR) software.Results: We found that the del/del genotype of A3B deletion significantly increased NSCLC risk.Compared with individuals carrying the ins/ins genotype of A3B deletion, individuals with the del/del genotype had a 2.36 times increased risk of developing NSCLC after adjusting for confounding factors (OR =2.71, 95% CI: 1.67-4.42, P<0.001). A 3-factor gene-environment (A3B deletion, gender, and smoking) interaction model was found for NSCLC (OR =4.407, 95% CI: 1.174-16.549, P=0.028). Conclusions:We propose that the A3B deletion polymorphism can increase the risk of developing NSCLC, and their interactions with gender and smoking may contribute to the risk of NSCLC in the southern Chinese population.

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GATA3 and APOBEC3B are prognostic markers in adrenocortical carcinoma and APOBEC3B is directly transcriptionally regulated by GATA3

Cited by 9 publications

References 44 publications

Mutagenic Activity of AID/APOBEC Deaminases in Antiviral Defense and Carcinogenesis

Mutagenic Activity of AID/APOBEC Deaminases in Antiviral Defense and Carcinogenesis

Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors

APOBEC3B deletion polymorphism and lung cancer risk in the southern Chinese population

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