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Prognostic relevance of global histone H3 lysine 4 (H3K4) methylation in renal cell carcinoma
Author(s) -
Ellinger Jörg,
Kahl Philip,
Mertens Claudia,
Rogenhofer Sebastian,
Hauser Stefan,
Hartmann Wolfgang,
Bastian Patrick J.,
Büttner Reinhard,
Müller Stefan C.,
von Ruecker Alexander
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25250
Subject(s) - chromophobe cell , h3k4me3 , renal cell carcinoma , oncocytoma , medicine , cancer , clear cell , oncology , pathology , cancer research , biology , gene expression , biochemistry , promoter , gene
Epigenetic alterations play an important role in carcinogenesis. Recent studies suggested that global histone modifications are predictors of cancer recurrence in various tumor entities. Our study was performed to evaluate histone H3 lysine 4 mono‐methyl (H3K4me1), ‐di‐methyl (H3K4me2) and ‐trimethyl (H3K4me3) patterns in renal cell carcinoma (RCC) using a tissue microarray with 193 RCC (including 142 clear cell, 31 papillary, 10 chromophobe and 10 sarcomatoid RCC) and 10 oncocytoma specimens: H3K4me3 staining was more intense in papillary RCC, whereas H3K4me1 and H3K4me2 were similar in the diverse RCC subtypes. H3K4me2 and H3K4me3 levels were increased in oncocytoma. H3K4me1‐3 levels were inversely correlated with Fuhrman grading, pT stage, lymph node involvement and distant metastasis. Progression‐free survival and cancer‐specific survival were shorter in patients with low levels of H3K4me1‐3 in the univariate analysis, but we did not observe a significant correlation of a single modification in a multivariate model, which also included the established prognostic parameters TNM‐stage and Fuhrman grade. In comparison, the H3K4me score, which combined staining levels of the H3K4 modifications, was an independent predictor of RCC progression‐free survival. Our study on H3K4 methylation supports the concept of global histone modifications as potential cancer prognosis markers.