The discovery of Rous sarcoma virus (RSV) led to the identification of cellular Src (c-Src), a non-receptor tyrosine kinase, which has since been implicated in the development of numerous human cancers. c-Src has been found to be highly activated in colon cancers, particularly in those metastatic to the liver. Studies of the mechanism of c-Src regulation have suggested that c-Src kinase activity is downregulated by phosphorylation of a critical carboxy-terminal tyrosine (Tyr 530 in human c-Src, equivalent to Tyr 527 in chicken Src) and have implied the existence of activating mutations in this C-terminal regulatory region. We report here the identification of a truncating mutation in SRC at codon 531 in 12% of cases of advanced human colon cancer tested and demonstrate that the mutation is activating, transforming, tumorigenic and promotes metastasis. These results provide, for the first time, genetic evidence that activating SRC mutations may have a role in the malignant progression of human colon cancer.

Background: Differences in cardiac remodeling after mitral valve (MV) surgery between the sexes is poorly understood. Inferior outcomes for females undergoing MV surgery compared with males have been suggested in the literature, although causative factors behind this discrepancy have not been identified. Materials and Methods: In this propensity-matched, retrospective, single-center study, we sought to identify the impact that sex may have on cardiac remodeling and long-term outcomes to better inform clinical decision-making in MV surgical intervention. Outcomes were compared between males and females undergoing MV replacement (MVR) between 2004 and 2018. The primary outcome was cardiac remodeling 1 year postoperatively. Secondary outcomes included mortality, stroke, myocardial infarction (MI), reoperation of the MV, and rehospitalization. Results: A total of 311 males and 311 females were included after propensity matching. Both groups demonstrated significant improvement in left atrial remodeling, although only males demonstrated a significant degree of improved left ventricular remodeling while their female counterparts did not. Mortality rates were relatively equivalent between the two groups, although males were more likely to develop sepsis and require rehospitalization due to MI. Conclusions: There has been little research exploring the differences in cardiac remodeling between the sexes after MVR. The results of this study have suggested that MVR is equally safe for both sexes and has demonstrated a difference in the heart's ability to remodel after MVR. The significance of this difference has the potential to result in largely different clinical outcomes for males and females. Further study is necessary to fully elucidate this relationship.

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