Identification of Genomic Determinants of Response of Metastatic Disease to Taxol and Adriamycin
Abstract
Human breast cancer genesis and progression is caused by the aberrant function of genes that positively and negatively regulate aspects of cell proliferation, apoptosis, genome stability, angiogenesis, invasion and metastasis( 1). Discovery and functional assessment of these genes is critical for understanding the biology of cancer, and for clinical applications including early cancer detection and improved prediction of cancer risk, disease course and response to therapy. Although many different events can cause aberrant gene function, chromosomal aberrations resulting in changes in gene dosage or structure play important roles. Interestingly, there is remarkable variability in the degree to which tumor genomes are aberrant at the chromosomal level. Some tumors have few chromosomal aberrations, while in others there may be dozens. Furthermore, the aberration spectrum typically differs substantially among clinically similar tumors. It is likely that many of these aberrations are accumulated by chance during the proliferation of cells with substantial genome instability and do not contribute to substantially to the tumor phenotype. However, some specific aberrations occur frequently and very likely do affect function. Extensive catalogues of recurrent abnormalities in a wide range of solid tumors have been compiled from cytogenetic(2) and CGH studies(3). These analyses show that tumors that arise in different anatomical sites differ significantly in recurrent aberration composition, as do histologically distinct tumors that arise in the same anatomic location(4-6). The spectrum of aberrations also varies with the genetic makeup of the patient. For example, recurrent aberrations in tumors that arise in individuals with BRCA1 mutations differ from those in tumors from BRCA2 carriers and from those in tumors that arise spontaneously(7).
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2002
- Accession Number
- ADA414174
Entities
People
- Joe W. Gray
Organizations
- University of California, San Francisco