Single-cell Sequencing Reveals Variants in ARID1A, GPRC5A and MLL2 Driving Self-renewal of Human Bladder Cancer Stem Cells

Yang, Zhao; Li, Chong; Fan, Zusen; Liu, Hongjie; Zhang, Xiaolong; Cai, Zhiming; Xu, Liqin; Luo, Jian; Huang, Yi; He, Luyun; Liu, Chunxiao; Wu, Song

doi:10.1016/j.eururo.2016.06.025

Cited by 115 publications

(89 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There may be multiple molecular subtypes in the same tumor, which may be an important factor affecting the accuracy of the molecular subtyping prediction system. With the rapid development of single-cell high-throughput sequencing (46,55,56), mass spectrometric detection (57), immune analysis (58,59), and other technologies, the accuracy of the molecular subtyping prediction system will be further improved (Figure 4). Compared with traditional pathological classification, molecular subtyping offers a more comprehensive analysis of the genome, transcriptome and non-coding RNA, providing important guidance for BC adjuvant chemotherapy, targeted therapy and immunotherapy.…”

Section: Mibc Molecular Subtypingmentioning

confidence: 99%

Traditional Classification and Novel Subtyping Systems for Bladder Cancer

Zhu

Xiao-mi

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Bladder cancer is the most common tumor in the urinary system, with approximately 420,000 new cases and 160,000 deaths per year. The European Organization for Research and Treatment of Cancer (EOTRC) classifies non-muscular invasive bladder cancer (NMIBC) into low-risk, medium-risk and high-risk groups based on a comprehensive analysis of NMIBC pathological parameters and the risk of recurrence and progression to muscular invasive bladder cancer (MIBC). Traditional classification systems are based on pathologic grading, staging systems, and clinical prognosis. However, the pathological parameters of the tumor cannot fully reflect the "intrinsic characteristics" of bladder cancer, and tumors with a similar pathology exhibit different biological behaviors. Furthermore, although the traditional classification system cannot accurately predict the risk of recurrence or the progression of bladder cancer patients (BCs) individually, this method is widely used in clinical practice because of its convenient operation. With the development of sequencing and other technologies, the genetics-based molecular subtyping of bladder cancer has become increasingly studied. Compared with the traditional classification system, it provides more abundant tumor biological information and is expected to assist or even replace the traditional typing system in the future.

show abstract

Section: Mibc Molecular Subtypingmentioning

confidence: 99%

Traditional Classification and Novel Subtyping Systems for Bladder Cancer

Zhu

Xiao-mi

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Little overlapping of somatic exonic mutations existed between the two cancers showing the normal urothelial stem cell origin [5]. The authors did not address how their findings could reconcile with recent data from mouse lineage tracing suggesting divergent progenitor cells for bladder cancer variants [6] (and see below).…”

mentioning

confidence: 86%

“…In addition, the authors identified 21 mutated genes in bladder cancer stem cells, of which six were novel. Finally, the authors demonstrated that mutation of ARID1A, GPRC5A, and MLL2 all together, but not singly or in various combinations, conferred stem-cell characteristics to bladder cancer non-stem cells [5].…”

mentioning

confidence: 98%

“…Studies of other cancer types suggest that conventional therapies primarily target the bulk tumor cells, leaving stem/progenitor cells largely untouched and leading to ''escaped clones'' and treatment failure. In this issue of European Urology, Yang and colleagues [5] report on their use of single-cell sequencing of CD44-differentially sorted normal urothelial stem cells, normal urothelial non-stem cells, bladder cancer stem cells, and bladder cancer non-stem cells [5]. A total of 59 individual cells from three bladder cancer patients (2 with pT1 and 1 with pT2; 5 cells/group/patient) were subjected to exome sequencing.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Attention to Detail by Single-cell Sequencing

2017

European Urology

View full text Add to dashboard Cite

“…The methylation of histone H3K4me3, and the expression of downstream GATA4 , ETS1 were enhanced significantly in recurrent BC tissues and patients with higher expression of GATA4 and ETS1 has a shorter survival time, which revealed that H3K4me3 and the expression of GATA4 and ETS1 were promising targets for monitoring and treatment of BC recurrence . Yang et al identified 21 key altered genes in BCSCs including five novel mutated genes ( GPRC5A, MKL1, PAWR, PITX2, and RGS9BP ) in BC by single‐cell sequencing, and found that the co‐mutations of ARIDA1, GPRC5A, and MLL2 played a critical role in maintaining the stemness of bladder cancer stem cells . Above results provided more possibilities for the targeted therapy of BC.…”

Section: Research Front Of Precision Diagnosis In Bladder Cancermentioning

confidence: 99%

Hope and challenge: Precision medicine in bladder cancer

Jiang

Tao

et al. 2019

Cancer Medicine

Self Cite

View full text Add to dashboard Cite

Bladder cancer (BC) is a complex disease and could be classified into nonmuscle‐invasive BC (NMIBC) or muscle‐invasive BC (MIBC) subtypes according to the distinct genetic background and clinical prognosis. Until now, the golden standard and confirmed diagnosis of BC is cystoscopy and the major problems of BC are the high rate of recurrence and high costs in the clinic. Recent molecular and genetic studies have provided perspectives on the novel biomarkers and potential therapeutic targets of BC. In this article, we provided an overview of the traditional diagnostic approaches of BC, and introduced some new imaging, endoscopic, and immunological diagnostic technology in the accurate diagnosis of BC. Meanwhile, the minimally invasive precision treatment technique, immunotherapy, chemotherapy, gene therapy, and targeted therapy of BC were also included. Here, we will overview the diagnosis and therapy methods of BC used in clinical practice, focusing on their specificity, efficiency, and safety. On the basis of the discussion of the benefits of precision medicine in BC, we will also discuss the challenges and limitations facing the non‐invasive methods of diagnosis and precision therapy of BC. The molecularly targeted and immunotherapeutic approaches, and gene therapy methods to BC treatment improved the prognosis and overall survival of BC patients.

show abstract

Single-cell Sequencing Reveals Variants in ARID1A, GPRC5A and MLL2 Driving Self-renewal of Human Bladder Cancer Stem Cells

Abstract: Human bladder cancer stem cells show the high level of consistency and may derived from bladder epithelial stem cells or bladder cancer non-stem cells. Mutations of ARID1A, GPRC5A and MLL2 grant bladder cancer non-stem cells the capability of self-renewal.

Cited by 115 publications

References 9 publications

Traditional Classification and Novel Subtyping Systems for Bladder Cancer

Traditional Classification and Novel Subtyping Systems for Bladder Cancer

Attention to Detail by Single-cell Sequencing

Hope and challenge: Precision medicine in bladder cancer

Contact Info

Product

Resources

About