IDENTIFICATION OF TUMOR SUPPRESSOR GENES IN AN ACUTE MYELOID LEUKAEMIA MODEL

摘要

The present invention comprises a method method to identify tumor suppressor genes by detecting genes in a mouse retroviral insertion mutagenesis model which expression is inhibited by methylation of the viral insertion or the VIS-flanking gene. This is preferably accomplished by first randomly cutting the mouse genomic DNA, immunoprecipitating the methylated DNA and amplifying the VIS-flanking DNA by inverse PCR, optionally followed by cloning and sequencing of the amplicons. Next to the already known tumor suppressor genes Smad1 and Mad1-like, several putative tumor suppressor genes have been found. The tumor suppressing properties of these genes, as indicated in Table 3 also form part of the present invention. Further use of these genes and/or its substrates or downstream products, for diagnosis and therapy of cancer, preferably AML is envisaged.