Prognostic relevance of global histone H3 lysine 4 (H3K4) methylation in renal cell carcinoma

被引：113

作者：

Ellinger, Joerg ^{[1
]}

Kahl, Philip ^{[2
]}

Mertens, Claudia ^{[1
]}

Rogenhofer, Sebastian ^{[1
]}

Hauser, Stefan ^{[1
]}

Hartmann, Wolfgang ^{[2
]}

Bastian, Patrick J. ^{[3
]}

Buettner, Reinhard ^{[2
]}

Mueller, Stefan C. ^{[1
]}

von Ruecker, Alexander ^{[2
]}

机构：

[1] Univ Klinikum Bonn, Klin & Poliklin Urol, D-53105 Bonn, Germany

[2] Univ Klinikum Bonn, Inst Pathol, D-53105 Bonn, Germany

[3] Klinikum Univ Munchen Grosshadern, Urol Klin & Poliklin, D-81377 Munich, Germany

来源：

INTERNATIONAL JOURNAL OF CANCER | 2010年 / 127卷 / 10期

关键词：

histone; methylation; H3K4; renal cell carcinoma; prognosis; MODIFICATIONS PREDICT PROGNOSIS; CANCER RECURRENCE; DNA-METHYLATION; BREAST-CANCER; ACETYLATION; PATTERN;

D O I：

10.1002/ijc.25250

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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 monomethyl (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.

引用

页码：2360 / 2366

页数：7

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