CHAPTER 1 A New Approach to an Old Problem

The role of genetic changes in neoplasia has been amatter of debate formore than 100 years. The earliest systematic study of cell division in malignant tumors was made in 1890 by the German pathologist David vonHansemann. He drew attention to the frequent occurrence of aberrantmitoses in carcinomabiopsies and suggested that this phenomenon could be used as a criterion for diagnosing the malignant state. His investigations as well as other studies associating nuclear abnormalities with neoplastic growth were, a quarter of a century later, forged into a systematic somatic mutation theory of cancer, which was presented in 1914 by Theodor Boveri in his famous book Zur Frage der Entstehung maligner Tumoren. According to Boveri’s hypothesis, chromosome abnormalities were the cellular changes causing the transition from normal to malignant proliferation. For a long time, Boveri’s remarkably prescient idea, the concept that neoplasia is brought about by an acquired genetic change, could not be tested. The study of sectioned material yielded only inconclusive results and was clearly insufficient for the examination of chromosome morphology. Technical difficulties thus prevented reliable visualization of mammalian chromosomes, in both normal and neoplastic cells, throughout the entire firs