Hypomethylation of PRAME is responsible for its aberrant overexpression in human malignancies.
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.
Schenk
Tino
T
Department of Cell and Molecular Biology, Leibniz Institute for Natural Products Research and Infection Biology-Hans Knoell Institute, 07745 Jena, Germany.
Stengel
Sven
S
Goellner
Stefanie
S
Steinbach
Daniel
D
Saluz
Hans Peter
HP
D024506:5' Flanking Region; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
D000951:Antigens, Neoplasm; C404944:PRAME protein, human