Determinants of clinical outcome in cancer. The schematic outlines the interaction between germline genetic background and somatic alterations in influencing cancer outcome. Germline variations may result in differences between individuals in drug metabolizing activities, cancer pathways, and development of distinct molecular subtypes of cancer (top boxes). Alternatively, somatic alterations can cause differences in histopathology, gene expression, and gene amplifications and deletions (bottom boxes). Overlaid upon this germline/somatic interaction is the specific choice of treatment regimen. All these factors interplay to ultimately determine patient outcome (Kaplan-Meier survival curve on right). Pictures of human figures were adapted from http://commons.wikimedia.org/wiki/Image:Wikicouple.svg. Pictures of FISH images and Kaplan-Meier survival curves were generated in the author's laboratory and previously used in .