Phosphorylated H2AX in Noninvasive Low Grade Urothelial Carcinoma of the Bladder: Correlation With Tumor Recurrence

Cheung, Wang L.; Albadine, Roula; Chan, Theresa; Sharma, Rajni; Netto, George J.

doi:10.1016/j.juro.2008.10.146

Cited by 28 publications

(19 citation statements)

References 14 publications

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“…Recently, we reported that global H3K4 and H3K20 methylation were decreased in BCa compared to normal urothelial tissue, and that global H4K20me3 levels were predictive for BCa-related death [7]. Low levels of histone H2AX phosphorylation at serine 139 have been identified as a risk factor for recurrence of NMIBC [9]; activation of the DNA damage response pathway results in H2AX phosphorylation and thereby recruits DNA repair effectors (e.g. BRCA1) [23].…”

Section: Discussionmentioning

confidence: 99%

“…Barbisan et al [8] reported in a small-scaled study decreased levels of H3K9Ac in recurrent papillary urothelial neoplasm of low malignant potential compared to non-recurrent papillary urothelial neoplasm of low malignant potential. Furthermore, phosphorylation of histone H2AX at serine 139 was correlated with a reduced risk of BCa recurrence following transurethral resection [9]. …”

Section: Introductionmentioning

confidence: 99%

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Alterations of Global Histone H3K9 and H3K27 Methylation Levels in Bladder Cancer

et al. 2014

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Background: Epigenetic alterations, including histone modifications, play an important role during carcinogenesis. This study was designed to systematically investigate histone H3K9 and H3K27 methylation levels in bladder cancer (BCa) tissue. Methods: A tissue microarray with urothelial BCa (150 non-muscle-invasive BCa, NMIBC; 121 muscle-invasive BCa, MIBC; 31 metastatic BCa, MET) and normal urothelium (29, CTRL) specimen was used to determine the global levels of H3K9 and H3K27 mono-, di- and tri-methylation. Results: Global levels of H3K9 and H3K27 methylation were significantly higher in CTRL than in BCa, and levels in NMIBC were higher compared to MIBC. Histone methylation levels of MET resembled MIBC. We observed furthermore a correlation of histone methylation levels with pT stage (H3K9me1, H3K9me2, H3K9me3, H3K27me1, H3K27me3) and grade (H3K9me2, H3K9me3, H3K27me1) in NMIBC. H3K9me1, H3K9me3, H3K27me1 and H3K27me3 levels were also correlated with pT stage in MIBC. Histone modifications were not associated with recurrence-free or cancer-specific survival. Conclusions: Global histone H3K9 and H3K27 methylation levels are altered in BCa.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alterations of Global Histone H3K9 and H3K27 Methylation Levels in Bladder Cancer

et al. 2014

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“…66 In another study, gH2AX positivity was found to be associated with a lower rate of tumor recurrence in urothelial cancer patients, suggesting the prevention of accumulation of genomic damage. 67 In addition, Toyoda et al 68 suggested that gH2AX may be a potential biomarker for the early detection of genotoxic bladder carcinogens. In another study, gH2AX was found to play a role in the differentiation status of thyroid cancer.…”

Section: Gh2ax Studies: Biosamplingmentioning

confidence: 99%

gamma-H2AX: Can it be established as a classical cancer prognostic factor?

Palla¹,

Karaolanis

Katafigiotis

et al. 2017

Tumour Biol.

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Double-strand breaks are among the first procedures taking place in cancer formation and progression as a result of endogenic and exogenic factors. The histone variant H2AX undergoes phosphorylation at serine 139 due to doublestrand breaks, and the gamma-H2AX is formatted as a result of genomic instability. The detection of gamma-H2AX can potentially serve as a biomarker for transformation of normal tissue to premalignant and consequently to malignant tissues. gamma-H2AX has already been investigated in a variety of cancer types, including breast, lung, colon, cervix, and ovary cancers. The prognostic value of gamma-H2AX is indicated in certain cancer types, such as breast or endometrial cancer, but further investigation is needed to establish gamma-H2AX as a prognostic marker. This review outlines the role of gamma-H2AX in cell cycle, and its formation as a result of DNA damage. We investigate the role of gamma-H2AX formation in several cancer types and its correlation with other prognostic factors, and we try to find out whether it fulfills the requirements for its establishment as a classical cancer prognostic factor.

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“…Mesane tümöründe histon modifikasyonlarının prognostik değerine bakıldığında, düşük malign potansiyelli papiller ürotelyal neoplazmda azalmış H3K9ac seviyesi artmış rekürrens eğilimi ile ilişkili olarak bulunmuştur (54). Bunun aksine, histon H2AX'ın (H2AXS139Ph) serin 139'unun fosforilasyonu transüretral rezeksiyon (TUR) sonrası düşük rekürrens riski ile ilişkilidir (55). Farklı evrelerdeki mesane tümörlü hastaların dokularının incelendiği yakın zamandaki bir çalışma H3K4me1, H4K20me1, H4K20me2 ve H4K20me3 immünekspresyon düzeylerinin ileri patolojik evre ile korele olduğunu; H4K20me3'ün kas invaziv mesane tümörlü hastalarda hastalığa spesifik sağkalımın bağımsız prognostik prediktörü olduğu gösterilmiştir (56).…”

Section: Epigenetik Belirteçlerin Prognostik öNemiunclassified