CALCA and cancer: Notably, LSL-KrasG12D; p48-Cre mice present fewer background tumors at a variety of sites than LSL-KrasG12D; Pdx-1-Cre mice do.103 The validity of the KC mouse model has been questioned on the basis that most cancers arise from somatic mutations that occur during adulthood.104 However, recent studies in various human cancers have changed this paradigm.105 Specifically, several driver mutations in hematological malignancies and solid tumors occur very early in life, sometimes during gestation, and clonal expansion occurs decades before cancer diagnosis.105