UCSD Adjunct Professor Pathology; Professor, Sanford Burnham Medical Research Institute
Ph.D., University of Madrid, Spain
Dr. Perucho studies tumors from the intestinal tract (i.e. colon, and stomach) that sometimes develop when the cell machinery preserving the integrity of the genome, like computer spelling programs that detect errors and correct them, is not working properly. When these corrector genes (mutators) are inactivated, the mutations that occur in all normal cells accumulate in large numbers because they are not repaired. This originates a remarkable genomic instability and cancer eventually develops when mutations occur in some cancer genes, such as the oncogenes and tumor suppressor genes. Recently, it has become clear that some of the mutator genes are not inactivated by mutations (mutator mutations) but by epigenetic silencing. This results as a consequence of the disintegration of the epigenetic code, an unexplored process that is strongly associated to aging. These studies have clinical applications. For instance, many hereditary colon tumors originate by mutations in mutator genes that are transmitted from generation to generation. Molecular diagnosis of the deficient mutator genes determines which members of these families will be affected in the future. Identification of tumors with this kind of genomic instability is also useful to detect familial cancer patients and to predict survival.
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