The observed differences in survival among animals with localized disease could be the result of reduced or delayed invasive potential of 17KPC primary tumors. Thorough histological step sectioning of all primary tumors and adjacent tissues obtained in the study demonstrated equivalent evidence of invasion between KPC and 17KPC animals at the time of euthanasia (data not shown). This suggests that local invasion is a common endpoint in our survival study, but requires more time to develop in 17KPC mice, resulting in the longer survival and larger tumors of localized 17KPC mice compared to localized KPC mice. Localized pancreatic cancer in mice can cause morbidity with biliary obstruction and jaundice (evident in the ears, footpads, or pancreas) or gastrointestinal (GI) obstruction, as seen by gross abdominal distension and GI lumen distension upstream of an adhesion with the absence of downstream luminal contents on necropsy. While these features were commonly observed in KPC mice, 17KPC mice never presented with any form of GI or biliary obstruction (Supplementary Figure 8). Other characteristics of tumor presentation such as the presence of adhesions to adjacent organs, intraperitoneal bleeding, jaundice or ascites demonstrated no significant differences between KPC and 17KPC mice (Supplementary Figure 8). Together, these in vivo findings suggest that loss of the mir-17~92 cluster may impact PDAC cell invasion, a feature associated with later stages of disease.