Prognostic and diagnostic relevance of hypermethylated in cancer 1 (HIC1) CpG island methylation in renal cell carcinoma

被引：30

作者：

Eggers, H. ^{[1
]}

Steffens, S. ^{[1
]}

Grosshennig, A. ^{[2
]}

Becker, J. U. ^{[4
]}

Hennenlotter, J. ^{[3
]}

Stenzl, A. ^{[3
]}

Merseburger, A. S. ^{[1
]}

Kuczyk, M. A. ^{[1
]}

Serth, J. ^{[1
]}

机构：

[1] Hannover Med Sch, Dept Urol, D-30625 Hannover, Germany

[2] Hannover Med Sch, Inst Biometry, D-30625 Hannover, Germany

[3] Univ Tubingen, Dept Urol, D-72074 Tubingen, Germany

[4] Hannover Med Sch, Dept Pathol, D-30625 Hannover, Germany

来源：

INTERNATIONAL JOURNAL OF ONCOLOGY | 2012年 / 40卷 / 05期

关键词：

renal cell carcinoma; Hypermethylated in Cancer 1; methylation; Pyrosequencing; CpG island; recurrence-free survival; TUMOR-SUPPRESSOR GENE; PROMOTER HYPERMETHYLATION; KIDNEY CANCER; EXPRESSION; P53; LOCUS; D17S5;

D O I：

10.3892/ijo.2012.1367

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The tumour suppressor gene hypermethylated in cancer I (HIC1) is a transcriptional repressor, which functionally cooperates with p53. Loss of HIC1 function is associated with the development of various tumor entities. The aim of this study was to elucidate the relevance of CpG island (CGI) methylation of HIC1 in renal cell carcinoma (RCC). DNA methylation of HIC1 was analysed in a total of 98 tumor and 70 tumor adjacent normal specimens. After conducting bisulfite conversion, relative methylation levels were quantitated using pyrosequencing. Relative methylation values were compared for paired tumor and normal specimen and for correlation with clinico-pathologic and follow-up data of patients. Tumor-specific hypermethylation could not be detected for the subregion of the HIC1 - CGI analyzed in this study. Comparing the level of methylation in tumors to clinicopathological data solely, patients without lymph node metastases demonstrated a higher level of methylation compared to patients with lymph node metastases (p=0.030). Patients recurrence-free survival (p=0.0074) both in univariate as well as bivariate Cox regression analysis. This study identifies HIC1 hypermethylation in tumors as an independent predictor of reduced recurrence-free survival, which fits into our current understanding of hypermethylated HIC1 being a marker for poor prognosis. Therefore, HIC1 - CGI methylation could be a candidate marker to improve individualized therapy and risk stratification.

引用

页码：1650 / 1658

页数：9

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