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Open Access 01-12-2007 | Research

RASSF1A promoter methylation and expression analysis in normal and neoplastic kidney indicates a role in early tumorigenesis

Authors: Inga Peters, Kristina Rehmet, Nadine Wilke, Markus A Kuczyk, Jörg Hennenlotter, Tyark Eilers, Stefan Machtens, Udo Jonas, Jürgen Serth

Published in: Molecular Cancer | Issue 1/2007

Abstract

Background

Epigenetic silencing of the RAS association domain family 1A (RASSF1A) tumor suppressor gene promoter has been demonstrated in renal cell carcinoma (RCC) as a result of promoter hypermethylation. Contradictory results have been reported for RASSF1A methylation in normal kidney, thus it is not clear whether a significant difference between RASSF1A methylation in normal and tumor cells of the kidney exists. Moreover, RASSF1A expression has not been characterized in tumors or normal tissue as yet.

Results

Using combined bisulfite restriction analysis (COBRA) we compared RASSF1A methylation in 90 paired tissue samples obtained from primary kidney tumors and corresponding normal tissue. Bisulfite sequence analysis was carried out using both pooled amplicons from the tumor and normal tissue groups and subclones obtained from a single tissue pair. Expression of RASSF1A was analyzed by the use of tissue arrays and immunohistochemistry. We found significantly increased methylation in tumor samples (mean methylation, 20%) compared to corresponding normal tissues (mean methylation, 11%; P < 0.001). Densely methylated sequences were found both in pooled and individual sequences of normal tissue. Immunohistochemical analysis revealed a significant reduced expression of RASSF1A in most of the tumor samples. Heterogeneous expression patterns of RASSF1A were detected in a subgroup of histologically normal tubular epithelia.

Conclusion

Our methylation and expression data support the hypothesis that RASSF1A is involved in early tumorigenesis of renal cell carcinoma.

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Title: RASSF1A promoter methylation and expression analysis in normal and neoplastic kidney indicates a role in early tumorigenesis
Authors: Inga Peters
Kristina Rehmet
Nadine Wilke
Markus A Kuczyk
Jörg Hennenlotter
Tyark Eilers
Stefan Machtens
Udo Jonas
Jürgen Serth
Publication date: 01-12-2007
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2007
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/1476-4598-6-49

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Abstract

Background

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