RT Book, Section A1 Brock, Malcolm A1 Wrangle, John A2 Morita, Shane Y. A2 Balch, Charles M. A2 Klimberg, V. Suzanne A2 Pawlik, Timothy M. A2 Posner, Mitchell C. A2 Tanabe, Kenneth K. SR Print(0) ID 1145755393 T1 Cancer Epigenetics T2 Textbook of Complex General Surgical Oncology YR 2018 FD 2018 PB McGraw-Hill Education PP New York, NY SN 9780071793315 LK hemonc.mhmedical.com/content.aspx?aid=1145755393 RD 2024/10/07 AB Conrad Hal Waddington is usually credited with modifying the Greek word “epigenesis,” which described a theory of development, into a new term “epigenetics” to mean “the causal interactions between genes and their products which bring the phenotype into being.”1 Waddington described an “epigenetic landscape” usually as a system of bifurcating valleys through which a cell, depicted alternatively as water or a roulette ball, flows or rolls toward the sea constantly making binary choices on its way.2 Waddington explained how genes were responsible for creating this “epigenetic landscape” of valleys since these genes were positioned on the underside of the landscape and attached to it by a series of “guy ropes” much like how pegs with ropes determine the shape of a tent's canopy. Thus, genes were ultimately responsible for the motley array of crevices, valleys, and hills in the canopy through which a ball could follow downhill as it embarked on its developmental pathway of differentiation. In addition to Waddington, other leading biologists of the time, including Ernest Hadorn, Richard Goldschmidt, and Julian Huxley, also saw a relationship between genes and their action to development during a period when embryology and developmental biology were very disparate disciplines.4 Thus, the term “epigenetics” proved durable not only because it provided a convenient explanation of how expressed genes informed developmental decisions of a cell, but also because it brought together the two disciplines of Mendelian genetics and embryology. In time, epigenetics has become used not only to explain heritable changes in development, but also to understand diverse biological processes including normal aging, maternal X chromosome inactivation, as well as pathological states, such as cancer and neurodegenerative diseases.