Somatic Mutations Profile of a Young Patient With Metastatic Urothelial Carcinoma Reveals Mutations in Genes Involved in Ion Channels

Sharma, Jyoti; Deb, Barnali; George, Ige; Kapil, Shruthi; Coral, Karunakaran; Kakkar, Nandita; Pattanaik, Smita; Mandal, Arup Kumar; Mavuduru, Ravimohan; Kumar, Prashant

doi:10.3389/fonc.2019.00435

Cited by 14 publications

(6 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In particular, Sharma et al. ( 45 ) also reported that the deleterious mutation of SPEN p.S1078* emerges as a putative potential therapeutic target in advanced-stage urothelial carcinoma. Additionally, we first analyzed the relationships between mutated distributions with a specific signature in the COSMIC dataset in two TMEscore groups.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Genomic Characterization of Tumor Microenvironment and Relevant Signature in Clear Cell Renal Cell Carcinoma

Zhang

Zheng

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

PurposeTo systematically investigate the characterization of tumor microenvironment (TME) in clear cell renal cell carcinoma (ccRCC), we performed a comprehensive analysis incorporating genomic alterations, cellular interactions, infiltrating immune cells, and risk signature.Patients and MethodsMulti-omics data including RNA-seq, single-nucleotide variant (SNV) data, copy number variation (CNV) data, miRNA, and corresponding prognostic data were obtained from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database. The CIBERSORT algorithm was utilized to identify prognostic TME subclusters, and TMEscore was further quantified. Moreover, the mutational landscape of TCGA-KIRC was explored. Lastly, TIDE resource was applied to assess the significance of TMEscore in predicting immunotherapeutic benefits.ResultsWe analyzed the TME infiltration patterns from 621 ccRCC patients and identified 5 specific TME subclusters associated with clinical outcomes. Then, we found that TMEcluster5 was significantly related to favorable prognosis and enriched memory B-cell infiltration. Accordingly, we depicted the clustering landscape of TMEclusters, TMEscore levels, tumor mutation burden (TMB), tumor grades, purity, and ploidy in all patients. Lastly, TIDE was used to assess the efficiency of immune checkpoint blockers (ICBs) and found that the TMEscore has superior predictive significance to TMB, making it an essential independent prognostic biomarker and drug indicator for clinical use.ConclusionsOur study depicted the clustering landscape of TMEclusters, TMEscore levels, TMB, tumor grades, purity, and ploidy in total ccRCC patients. The TMEscore was proved to have promising significance for predicting prognosis and ICB responses, in accordance with the goal of developing rationally individualized therapeutic interventions.

show abstract

Section: Discussionmentioning

confidence: 99%

Comprehensive Genomic Characterization of Tumor Microenvironment and Relevant Signature in Clear Cell Renal Cell Carcinoma

Zhang

Zheng

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…CACNG1 (Voltage-dependent calcium channel gamma-1 subunit) encodes a muscle-specific isoform of the Ca 2+ channel gamma subunit. CACNG1 is increased in the lamina propria of the old rats, and the deleterious mutation is discovered in a young patient with metastatic urothelial carcinoma 33,34 . DUSP13 (Dual specificity protein phosphatase 13) encodes two atypical DUSPs, DUSP13B/TMDP and DUSP13A/MDSP, that are specifically expressed in testis and skeletal muscle respectively 35,36 .…”

Section: Discussionmentioning

confidence: 99%

Tissue-specific regulatory mechanism of LncRNAs and methylation in sheep adipose and muscle induced by Allium mongolicum Regel extracts

Xue

Erdene

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Allium mongolicum Regel (A. mongolicum) is a perennial and xerophytic Liliaceous allium plant in high altitude desert steppe and desert areas. Feeding A. mongolicum greatly reduced unpleasant mutton flavor and improves meat quality of sheep. We analyzed epigenetic regulatory mechanisms of water extracts of A. mongolicum (WEA) on sheep muscle and adipose using RNA-Seq and whole-genome Bisulfite sequencing. Feeding WEA reduced differentially expressed genes and long non-coding RNAs (lncRNAs) between two tissues but increased differentially methylation regions (DMRs). LncRNA and DMR targets were both involved in ATP binding, ubiquitin, protein kinase binding, regulation of cell proliferation, and related signaling pathways, but not unsaturated fatty acids metabolism. Besides, tissue specific targets were involved in distinct functional annotations, e.g., Golgi membrane and endoplasmic reticulum for muscle lncRNA, oxidative phosphorylation metabolism for adipose lncRNA, dsRNA binding for muscle DMRs. Epigenetic regulatory networks were also discovered to discovered essential co-regulated modules, e.g., co-regulated insulin secretion module (PDPK1, ATP1A2, CACNA1S and CAMK2D) in adipose. The results indicated that WEA induced distinct epigenetic regulation on muscle and adipose to diminish transcriptome differences between tissues, which highlights biological functions of A. mongolicum, tissue similarity and specificity, as well as regulatory mechanism of mutton odor.

show abstract

“…Hitherto, negative results from clinical trials of targeted therapies suggest the need to identify novel biomarkers in regulating significant molecular mechanisms of ESCC progression ( Hirano and Kato, 2019 ). Alterations in ion channels, the membrane proteins that allow the influx and efflux of ions across membranes, have been reported in several tumors ( Sharma et al, 2019 ; Parthasarathi et al, 2022 ; Aydar et al, 2009 ; Chioni et al, 2010 ). Roles of ion channels in apoptosis and their potential in cell regulation and tumor progression were identified ( Comes et al, 2015 ; Fraser et al, 2014 ; Bustin et al, 2001 ).…”

Section: Introductionmentioning

confidence: 99%

Aberrations in ion channels interacting with lipid metabolism and epithelial–mesenchymal transition in esophageal squamous cell carcinoma

Parthasarathi

Mandal

George

et al. 2023

Front. Mol. Biosci.

Self Cite

View full text Add to dashboard Cite

Esophageal squamous cell carcinoma (ESCC) is the most prevalent malignant gastrointestinal tumor. Ion channels contribute to tumor growth and progression through interactions with their neighboring molecules including lipids. The dysregulation of membrane ion channels and lipid metabolism may contribute to the epithelial–mesenchymal transition (EMT), leading to metastatic progression. Herein, transcriptome profiles of patients with ESCC were analyzed by performing differential gene expression and weighted gene co-expression network analysis to identify the altered ion channels, lipid metabolism- and EMT-related genes in ESCC. A total of 1,081 differentially expressed genes, including 113 ion channels, 487 lipid metabolism-related, and 537 EMT-related genes, were identified in patients with ESCC. Thereafter, EMT scores were correlated with altered co-expressed genes. The altered co-expressed genes indicated a correlation with EMT signatures. Interactions among 22 ion channels with 3 hub lipid metabolism- and 13 hub EMT-related proteins were determined using protein–protein interaction networks. A pathway map was generated to depict deregulated signaling pathways including insulin resistance and the estrogen receptor-Ca2+ signaling pathway in ESCC. The relationship between potential ion channels and 5-year survival rates in ESCC was determined using Kaplan–Meier plots and Cox proportional hazard regression analysis. Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) was found to be associated with poor prognosis of patients with ESCC. Additionally, drugs interacting with potential ion channels, including GJA1 and ITPR3, were identified. Understanding alterations in ion channels with lipid metabolism and EMT in ESCC pathophysiology would most likely provide potential targets for the better treatment of patients with ESCC.

show abstract

Somatic Mutations Profile of a Young Patient With Metastatic Urothelial Carcinoma Reveals Mutations in Genes Involved in Ion Channels

Cited by 14 publications

References 31 publications

Comprehensive Genomic Characterization of Tumor Microenvironment and Relevant Signature in Clear Cell Renal Cell Carcinoma

Comprehensive Genomic Characterization of Tumor Microenvironment and Relevant Signature in Clear Cell Renal Cell Carcinoma

Tissue-specific regulatory mechanism of LncRNAs and methylation in sheep adipose and muscle induced by Allium mongolicum Regel extracts

Aberrations in ion channels interacting with lipid metabolism and epithelial–mesenchymal transition in esophageal squamous cell carcinoma

Contact Info

Product

Resources

About