Identification of Chromosomes Alterations in Primary Breast Cancer Using Premature Chromosome Condensation

摘要

Site-specific chromosome alterations have led to the identification of numerous genes directly involved in hematologic malignancies and selected solid tumors. Recognition of recurrent chromosome translocations are particularly informative because they can lead directly to the cloning and identification of genes which are altered in neoplasms. We hypothesize that, as been shown in other human tumors, early clinical breast cancers have site- specific, clonal chromosomal translocations which have not been identified previously. We are developing a new method, premature chromosome condensation (PCC),using mitotic Xenopus extracts that will allow us to obtain G-banded karyotypes from primary, uncultured breast cancer specimens. We have made such extracts and are optimizing conditions for use. We are also using a sensitive new technique termed spectral karyotyping (SKY), to identify site-specific, recurrent clonal chromosomal translocations in these PCC-induced karyotypes of primary breast cancer specimens. The problems in application at this point are technical and being addressed. Following the identification of recurrent, site specific chromosome alterations and particularly translocations in primary breast cancer, future investigations would target our long-term goal of identifying the genes directly involved at these chromosomal breakpoints.