Cellular genetic alterations: Models of breast and colon cancer

Genetic alterations at the cellular level (aggregate DNA content, karyotype) resulting in a malignant phenotype are often less precise but more accessible to analysis than those at the molecular level (gene structure, regulation, and expression) that are a step closer to the mechanistic basis for the disease. Quantitative DNA and cytogenetic analyses are widely applied in the diagnostic and prognostic evaluation of many human tumors and provide a necessary context for the detection and interpretation of molecular data. This chapter explores evidence relating cellular genetic changes to the biological and clinical aspects of two common human cancers, one for which precancerous lesions are well defined (colorectal neoplasia) and another, is the adenocarcinoma of the breast that lacks a generally accepted morphologic basis for the definition of a genetic pathway. The methodological approaches that permit the assessment of cellular genetic changes may serve as a bridge between traditional morphologic diagnosis and molecular analyses.