To avoid these pitfalls, we devised a novel method that can detect chromosomal translocations at the DNA level creating constant,Sauchinone predictable, and quantifiable amplicons. This technique, that we called GIPFEL utilizes the fact that genomic breakpoints are usually confined to defined chromosomal regions. Restriction digest of genomic DNA followed by circularization of resulting fragments will divide even large breakpoint regions into a manageable number of DNA circles. Only cells with translocations will create a ‘‘signature’’ circle that is uniquely characteristic for the nature of the underlying genomic aberration. These circles can be quantified by real-time PCR because the sequence of the corresponding ligation joint can be derived from the known genomic sequence and the respective location of the restriction sites within the breakpoint region. Hence corresponding amplicons of suitable size for real-time PCR can be designed. Positive amplification results do not only reveal the presence of a GSK-503 translocation but they also give topical information of the approximate localization of the genomic break. By selecting appropriate restriction enzymes even large breakpoint regions can be covered with relatively few primer/PCR reactions. Here we present a proof-of-principle study demonstrating that it is possible to detect the most commonly occurring translocations in childhood leukemia using small amounts of DNA without having to resort to long range PCR or unstable RNA. The GIPFEL method relies on the prior knowledge of the genomic region where breaks occur. As long as this information is available it can be adapted to any recurrent translocation. At the same time this is also a drawback of the technique. Breaks outside of the pre-defined genomic region will not be detected. Likewise, more complicated genomic rearrangements might elude discovery because they alter the predicted ligation joints. Translocations resulting from more complicated reshuffling of the genome have been described. During our study we serendipitously detected at breakpoint where material of chromosome 5 had been interspersed at the junction site of chromosome 11 and 19. Events of this type are the most likely explanation for the false negative rate in the present study.