The paradigms for molecular testing developed in the last century are more relevant than ever in today’s clinical practice. The regulatory framework of the three-dimensional (3D) genome architecture is a fundamental functional link between phenotypic features and the multitude of contributing molecular regulatory modalities. Diagnostic approaches based on chromatin conformations tend to reduce data complexity and sample processing time while adding essential clinical information not readily available with other diagnostic techniques.

A recent study demonstrated that long-range chromatin interactions with ectopically deregulated platelet-derived growth factor receptor A (PDGFRA) could be identified in glioma patients and cell lines with IDH1 R132H mutations. This data has since been confirmed and evaluated at high resolution by chromosome conformation capture EpiSwitch assay, with a readout based on MIQE-compliant qPCR.

Designed to the technical standards of the clinical-grade assay, the chromosome confirmation test has a strong potential to assist with the predictive prognosis for TKI (i.e., Gleevec) treatments. Regulatory alterations in genome architecture, associated with specified pathological conditions, can not be identified diagnostically with conventional genetic sequencing approaches.

The new frontier of conditional chromosomal confirmation associated with long-range interactions is defining the field of epigenetic regulatory control over the genome and the links to patient phenotype.