Pre-Nowell & Cairns
The earliest ideas about neoplastic evolution come from Boveri who proposed that tumors originated in chromosomal abnormalities passed on to daughter cells. In the decades that followed, cancer was recognized as having a clonal origin associated with chromosomal aberrations. .
Early mathematical modeling of cancer, by Armitage and Doll, set the stage for the future development of the somatic evolutionary theory of cancer. Armitage and Doll explained the cancer incidence data, as a function of age, as a process of the sequential accumulation of somatic mutations (or other rate limiting steps).
Advances in cytogenetics facilitated discovery of chromosome abnormalities in neoplasms, including the Philadelphia chromosome in chronic myelogenous leukemia and translocations in acute myeloblastic leukemia. Sequences of karyotypes replacing one another in a tumor were observed as it progressed . Researchers hypothesized that cancer evolves in a sequence of chromosomal mutations and selection and that therapy may further select clones.