Nat. Rev. Gastroenterol. Hepatol. doi:10.1038/nrgastro.2017.33 Figure 2 Two hypothetical scenarios for the origin of molecular subtypes Figure 2 | Two hypothetical scenarios for the origin of molecular subtypes. a | In this theoretical scenario, cancers in all the gastrointestinal organs start out as 'canonical' or 'ground state' epithelial subtype tumours. As these tumours progress and accumulate 'decisive events' that directly or indirectly influence tumour biology, they deviate from the epithelial state into divergent subtypes that can be classified as distinct entities. The shared original ground state can be organ-specific, but the resulting deviations from this state can be highly similar across tumours in the gastrointestinal organs and can be identified as analogous entities. b | In this theoretical scenario, tumours arise and progress from a fixed molecular subtype. Subtype-specific driver mutations and nongenetic factors (intrinsic or extrinsic) act early in the establishment of these cancers as the decisive events and there is no ground state to deviate from. The resulting phenotypes captured in a molecular profile can be identified across organs, with the commonality in early tumour-driving events determining their similarity. Bijlsma, M. F. et al. (2017) Molecular subtypes in cancers of the gastrointestinal tract Nat. Rev. Gastroenterol. Hepatol. doi:10.1038/nrgastro.2017.33