Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

By Yaoting Gui, Guangwu Guo, Yi Huang, Xueda Hu, A. Tang, Shengjie Gao, R. Wu, Chao Chen, Xianxin Li, Liang Zhou and 43 more. Nature Genetics, 2011

717 citations recorded by the source corpus.

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.

Subfields: Molecular Biology, Pulmonary and Respiratory Medicine, Surgery

View Paper: https://www.semanticscholar.org/paper/4dcc69c66b20494d34a1f0f0f929a3c59e4615a6

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Citations in the corpus

Lessons from the cancer genome. (2013, neutral): “Among the HATs, mutations affect CREBP and EP300 (Gui et al., 2011; Morin et al., 2011; Peifer et al., 2012).”
Cancer Genetics and Epigenetics: Two Sides of the Same Coin? (2012, background): “In addition, alternative splicing and mutations in MLL1, MLL2, and MLL3 genes have been identified in bladder, breast, and pancreatic cancers and in glioblastoma (Gui et al., 2011; Morin et al., 2011).”
The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part B: Prostate and Bladder Tumours. (2016, background): “Mutations in chromatin-remodelling and histonemodifying genes have been described in up to 89% of muscularis propria invasive bladder tumours [116,128].”
Epigenetic Determinants of Cancer. (2016, neutral): “…H3K4 Bladder TCC, hematopoietic, nonHodgkin lymphoma, B-cell lymphoma, prostate (primary) Translocation, mutation, aberrant expression (Gui et al. 2011; Morin et al. 2011) Histone modification enzymes EZH2 Histone methyltransferase H3K27 Breast, prostate, bladder, colon, pancreas,…”
Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology (2014, background): “In this regard, it is interesting to note that there appears to be a relatively high prevalence of mutations in histone- and chromatin-modifying genes in UC (3).”
TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal (2013, background): “TERT mutations are, therefore, the most frequently mutated genes yet identified in urothelial carcinoma of either the bladder or upper urinary tract (24).”
Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer. (2017, neutral): “NMIBC occurs mainly as papillary disease with frequent FGFR3 mutations, whereas MIBC has a more diverse mutation spectrum as well as copy-number instability (Balbas-Martinez et al., 2013; Cappellen et al., 1999; Gui et al., 2011; Knowles and Hurst, 2015; van Rhijn et al., 2001).”
Comprehensive Molecular Characterization of Urothelial Bladder Carcinoma (2014, neutral): “Weinstein(1a,1b), Scott Department of Urology, Baylor College of Medicine - Seth Lerner(2,3), Weiguo Jian(2,3), Sebrina Tello(2,3), Texas Cancer Research Biobank (TCRB), Baylor College of Medicine Michael Ittman(3,4), Patricia Castro(3,4), Whitney D.”