ObjectiveRecently, many tumor sequencing studies have inferred and reported on mutational signatures, short nucleotide patterns at which particular somatic base substitutions appear more often. A number of signatures reflect biological processes in the patient and factors associated with cancer risk. Our goal is to infer mutational signatures appearing in colon cancer, a cancer for which environmental risk factors vary by cancer subtype, and compare the signatures to those in adult stem cells from normal colon. We also compare the mutational signatures to others in the literature.ResultsWe apply a probabilistic mutation signature model to somatic mutations previously reported for six adult normal colon stem cells and 431 colon adenocarcinomas. We infer six mutational signatures in colon cancer, four being specific to tumors with hypermutation. Just two signatures explained the majority of mutations in the small number of normal aging colon samples. All six signatures are independently identified in a series of 295 Chinese colorectal cancers.