Human bladder cancers and normal bladder mucosa present the same hot spot of heterozygous chromosome-9 deletion

4591 Background: Bladder cancer is a common and deadly disease, but the molecular events leading to its initiation and progression are incompletely understood. We recently identified Ataxia-Telangiectasia Group D Associated (ATDC) as a novel oncogene which drives tumor proliferation and invasion in pancreatic carcinoma (Cancer Cell, 2009). In this study, we describe the role of ATDC as an oncogene in bladder cancer. Methods: To further determine the oncogenic role of ATDC, we generated ATDC transgenic (tg) mice in which ATDC expression was driven by a CMV promoter and characterized the resulting tumors. Results: Interestingly, the dominant phenotype in these mice was the development of both non-invasive and invasive urothelial carcinomas (9% and 20% respectively, average age of onset 10-12 months of age). Histologically, these tumors were indistinguishable from human urothelial carcinomas. Gene expression profiling of invasive tumors derived from ATDC tg mice demonstrated a marked overlap with gene signatures of human invasive bladder cancers. ATDC was the 11th most highly up-regulated gene in bladder cancers represented in the Oncomine gene expression database. Analysis of a human bladder cancer tissue microarray (311 samples) by IHC showed elevated expression in 70% (173/252) of muscle-invasive carcinomas, 22% (5/23) of papillary tumors and little or no expression in normal bladder urothelium. ATDC tg mouse bladder tumors demonstrated loss of p53 signaling and down-regulation of PTEN expression, which correlated with ATDC induced methylation of the PTEN promoter by DNMT3A. Furthermore, ATDC knock-down in invasive cancer cell lines resulted in decreased proliferation, invasion and reactivation of p53-mediated signaling and PTEN expression. Conclusions: ATDC is a novel oncogene that is highly expressed in human bladder cancers and is sufficient to drive the development of invasive bladder tumors in tg mice. The mechanism by which ATDC drives bladder cancer formation involves alterations in p53 and PTEN pathways known to be important in bladder tumorigenesis.

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A light- and electron-microscopic histopathological study of human bladder mucosa after intravesical resiniferatoxin application

BJU International ◽

10.1046/j.1464-410x.2001.02339.x ◽

2001 ◽

Vol 88 (4) ◽

pp. 355-360 ◽

Cited By ~ 20

Author(s):

C. Silva ◽

A. Avelino ◽

C. Souto-Moura ◽

F. Cruz

Keyword(s):

Histopathological Study ◽

Bladder Mucosa ◽

Electron Microscopic ◽

Human Bladder

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The telocytes/myofibroblasts 3-D network forms a stretch receptor in the human bladder mucosa. Is this structure involved in the detrusor overactive diseases?

Annals of Anatomy - Anatomischer Anzeiger ◽

10.1016/j.aanat.2018.01.009 ◽

2018 ◽

Vol 218 ◽

pp. 118-123 ◽

Cited By ~ 6

Author(s):

Maria-Giuliana Vannucchi ◽

Chiara Traini

Keyword(s):

Stretch Receptor ◽

Bladder Mucosa ◽

Human Bladder

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Differential diagnosis of human bladder mucosa pathologies in vivo with cross-polarization optical coherence tomography

Biomedical Optics Express ◽

10.1364/boe.6.001464 ◽

2015 ◽

Vol 6 (4) ◽

pp. 1464 ◽

Cited By ~ 33

Author(s):

Elena Kiseleva ◽

Mikhail Kirillin ◽

Felix Feldchtein ◽

Alex Vitkin ◽

Ekaterina Sergeeva ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Differential Diagnosis ◽

Optical Coherence ◽

Cross Polarization ◽

Bladder Mucosa ◽

Human Bladder

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ATDC as a novel oncogene in bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.269 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 269-269

Author(s):

Phillip Lee Palmbos ◽

Lidong Wang ◽

Huibin Yang ◽

Taylor Detzler ◽

Gina Ney ◽

...

Keyword(s):

Gene Expression ◽

Bladder Cancer ◽

Cancer Cell ◽

Pten Expression ◽

Cancer Tissue ◽

Bladder Tumors ◽

Human Bladder ◽

Urothelial Carcinomas ◽

Normal Bladder

269 Background: Bladder cancer is a common and deadly disease, but the molecular events leading to its initiation and progression are incompletely understood. We recently identified Ataxia-Telangiectasia Group D Associated (ATDC) as a novel oncogene which drives tumor proliferation and invasion in pancreatic carcinoma (Cancer Cell, 2009). In this study, we describe the role of ATDC as an oncogene in bladder cancer. Methods: To further determine the oncogenic role of ATDC, we generated ATDC transgenic (tg) mice in which ATDC expression was driven by a CMV promoter and characterized the resulting tumors. Results: The dominant phenotype in these mice was the development of both papillary and invasive urothelial carcinomas (9% and 20% respectively, average age of onset 10-12 months of age). Histologically, these tumors were indistinguishable from human urothelial carcinomas. Gene expression profiling of invasive tumors derived from ATDC tg mice demonstrated a marked overlap with gene signatures of human invasive bladder cancers. Analysis of a human bladder cancer tissue microarray (311 samples) showed elevated expression in 70% (173/252) of muscle-invasive carcinomas, whereas normal bladder had no expression. 22% (5/23) of papillary tumors also expressed elevated levels of ATDC. ATDC was the 11th most highly up-regulated gene in bladder cancers represented in the Oncomine gene expression database. ATDC tg mouse bladder tumors demonstrated loss of p53 signaling and down-regulation of PTEN expression, which was determined to be due to ATDC abrogation of p53 function by cytoplasmic sequestration and ATDC-mediated methylation of the PTEN promoter. Furthermore, ATDC knock-down in invasive cancer cell lines resulted in decreased proliferation, invasion and reactivation of p53-mediated signaling and PTEN expression. Conclusions: ATDC is a novel oncogene that is highly expressed in human bladder cancers and is sufficient to drive the development of invasive bladder tumors in tg mice. The mechanism by which ATDC drives bladder cancer formation involves alterations in p53 and PTEN pathways known to be important in bladder tumorigenesis.

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High-resolution mapping of the quantitative trait locus (QTLs) conferring resistance to false smut disease in rice

10.21203/rs.3.rs-325960/v1 ◽

2021 ◽

Author(s):

kumari neelam ◽

Kishor Kumar ◽

Amandeep Kaur ◽

Amit Kishore ◽

Pavneet Kaur ◽

...

Keyword(s):

Disease Resistance ◽

Yield Loss ◽

Hot Spot ◽

Crop Improvement ◽

Chromosome 9 ◽

Phenotypic Effect ◽

Ustilaginoidea Virens ◽

Rice False Smut ◽

Rice Chromosomes ◽

False Smut

Abstract Decoding the genetic mechanisms underlying disease resistance is of great importance for crop improvement. Rice false smut (RFS) is a major fungal disease caused by Ustilaginoidea virens that hampers the grain quality and yield of rice worldwide. It causes 2.8-49% global yield loss depending upon disease severity and varieties grown. In India, the severity of yield loss ranged from 2-75%. Keeping the economic importance of this disease, identification of the genes/QTLs governing disease resistance is of prime importance for the development of the linked markers and cloning of the genes. Here, we report mapping of QTLs using a recombinant inbred line (RIL) population derived from a cross between resistant line, RYT2668, and a highly susceptible variety, PR116. The population was evaluated for rice false smut disease under field conditions for three cropping seasons 2013, 2015, and 2016. A total of seven QTLs were mapped on rice chromosomes 2, 4, 5, 7, and 9 of rice using 2326 single nucleotide polymorphism (SNP) markers. Among them, a novel QTL qRFSr9.1 affecting total smut ball (TSB)/panicle on chromosome 9 exhibited the largest phenotypic effect. The prediction of putative candidate genes within the qRFSr9.1 spanned in 994.1Kb revealed four NBS-LRR domain-containing disease resistance proteins. We identified SNPs/Indels associated with the disease resistance which could be used for accelerating breeding programs using marker-assisted selection. In summary, our findings mark the ‘hot-spot’ region on rice chromosomes along with the identification of disease resistance genes in conferring resistance to the rice false smut disease.

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