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Hypomethylation of PRAME is responsible for its aberrant overexpression in human malignancies
Author(s) -
Schenk Tino,
Stengel Sven,
Goellner Stefanie,
Steinbach Daniel,
Saluz Hans Peter
Publication year - 2007
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20465
Subject(s) - dna methylation , biology , cancer research , methylation , myeloid leukemia , transfection , minimal residual disease , gene , leukemia , computational biology , microbiology and biotechnology , gene expression , immunology , genetics
The preferentially expressed antigen of melanoma (PRAME) is expressed at high levels in large fractions of human malignancies, e.g., acute myeloid leukemia. Therefore, PRAME is an important marker for diagnosis of various malignant diseases and a relevant parameter for monitoring minimal residual disease. It is supposed to be involved in tumorigenic processes. Because of these important aspects we investigated its transcriptional regulation in detail. Most relevant was a detailed DNA methylation analysis of the PRAME 5′ region by genomic sequencing in correlation with PRAME expression in various human patient samples and cell lines. In combination with DNA‐truncation/transfection experiments with respect to DNA methylation, we show that changes in the methylation pattern in defined parts of the regulatory regions of PRAME are sufficient for its upregulation in cells usually not expressing the gene. © 2007 Wiley‐Liss, Inc.