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Cancer Genetics and Genomics

Program Overview

Cancer is fundamentally a disease of disordered gene expression. Abnormal gene expression in cancer cells may be due to mutations within genes or closely linked DNA that regulates activity of those genes, deletions that remove various genes and gene regulatory sequences, amplification of genomic regions containing various genes, fusions of two genes by recombination between DNA sequences, or epigenetic changes - non-mutational modifications of DNA or of DNA-binding proteins that alter gene expression in a manner that can be transmitted to progeny cells over the course of multiple cell divisions. Furthermore, gene expression in cancer cells can be affected by perturbations in the machinery responsible for production or activity of proteins, such as systems that control the synthesis, modification, or degradation of proteins. If the changes regulate expression of other genes, as is often the case, there can be a large series of secondary effects on gene expression. It is the aggregate result of all these changes - multiple primary changes in gene expression plus the secondary changes, and beyond - that render a cell fully malignant.

The members of the Cancer Genetics and Genomics Program study all aspects of gene alterations in cancer. These studies include the discovery of mutations in genes and DNA that cause cancer; analysis of genomic changes and their functional consequences on gene expression; characterization of mechanisms that control protein production from genes; epigenetics; protein structure; and the analysis of large scale genomic data. Some researchers focus on specific genes in individual types of cancers, whereas others are involved in analyzing large numbers of genes and their expression in cancers both at diagnosis and

during progression of the disease. In practical terms, this research has implications for improved cancer diagnosis and prognostic assessment of tumors, therapeutic responsiveness of tumors, and pre-symptomatic screening for cancers, all through the discovery of changes in genes and their expression characteristic of those cancers. In addition, reversal or neutralization of the changes in gene expression offers attractive targets for the development of new anti-cancer drugs and therapeutic strategies.