) The purpose of the research proposed in this application is to develop and refine a methodology to detect cryptic chromosome inversions with a resolution of perhaps 3Mbp to 5Mbp and to begin to prepare such inversion probes for at least a few human chromosomes. The identification of translocation break-points and deleted regions of chromosomes by conventional cytogenetic techniques has led to a reasonably good understanding of several key genetic changes in a number of different cancers such as Burkitt's lymphoma and some leukemias and has even led to the discovery of new growth controlling genes. We suggest that some tumors where no obvious aberrations or no consistent aberrations are seen may contain cryptic inversions which have been impossible to detect. If so, knowledge of genes at the break points should be no less interesting than those for translocations. Aside from validating the need for inversion probes from the point of view of cancer cytogenetics, development of such probes would be very useful well beyond the cytogenetic scope of this proposal. For example, they could be used to determine the orientation of any cloned gene or sequence within a particular chromosome.
