Darryl Shibata

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  Reconstructing Human Cancer Progression From Private and Public Mutations
  Darryl Shibata

  The “start� of human tumorigenesis is difficult to study because most human tumors are undetectable until they reach about 1 cm in size (~1 billion cells). However, it may be possible to reconstruct even the first few divisions after tumor initiation through the analysis of somatic mutations in large present day tumors. Using coalescent theory, “public� mutations in the initiating cell will be present in all present day tumor cells. Assuming a simple exponential clonal expansion, “private� mutations that arise during the first few cell divisions will be present in most but not all present day tumor cells. The earlier a private mutation occurs, the greater its frequency in the final tumor. By sampling multiple regions from the same large human tumor, it is possible to identify public and private mutations, and then infer the early events after human tumor initiation.