Gatekeeper, caretaker, and landscaper mutations Gatekeeper, caretaker, and landscaper mutations. In the late 1990s, Kenneth Kinzler and Bert Vogelstein proposed a model of tumorigenesis based on their observations of the oncogenic mechanisms underlying hereditary colorectal cancer. Tumor-promoting genes were classified as gatekeepers, caretakers, and landscapers, according to their function. Gatekeeper genes encode proteins that regulate cell fate, be it proliferation, growth, arrest, death, or differentiation. Because deregulation of these mechanisms is likely to lead directly to abnormal growth, mutations in these genes correlate with the highest risk of cancer. Caretaker genes encode proteins that are responsible for guarding the integrity of the genome, with loss of function increasing the risk of acquiring mutations, for instance, in gatekeeper genes, that would lead to oncogenic growth. Mutations occurring in cells of the surrounding tissue stroma can create a microenvironment that is more permissive for tumorigenesis, and the associated genes were categorized as landscapers. As the functions of these genes are primarily supportive, in isolation, these mutations are much less penetrant. Source: Oncogenes and Tumor-Suppressor Genes, The Basic Science of Oncology, 5e Citation: Tannock IF, Hill RP, Bristow RG, Harrington L. The Basic Science of Oncology, 5e; 2016 Available at: http://hemonc.mhmedical.com/DownloadImage.aspx?image=/data/books/1791/tanbas5_ach7_f005.png&sec=124303832&BookID=1791&ChapterSecID=124303803&imagename= Accessed: November 01, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved