Endometrial, or uterine cancer, is the most common gynaecological cancer and affects mostly post-menopausal women. The population of women in Canada is aging, therefore the occurrence of uterine cancer will likely increase over the next few decades. The majority of low-risk uterine cancers are generally cured by hysterectomy with no additional chemotherapy needed. High-risk uterine cancers are often difficult to diagnose, and will require additional treatment after hysterectomy. These women tend to have metastatic disease and do not respond well to standard chemotherapy, thus leading to a low chance of survival. Therefore these types of aggressive diseases need to be thoroughly studied to understand the molecular differences to improve diagnoses and develop more effective treatments. In our research, we have used sequencing technology to discover a gene with a high frequency of mutations found in high risk endometrial cancers. This gene is part of an important enzyme complex, which is involved in directing many cellular processes. We will study the function of this enzyme complex and determine how these mutations can affect the growth of uterine cancer cells. This work will help improve diagnoses and potentially develop novel treatments to target this gene. In some cancer types, tumour DNA can be detected in the blood of cancer patients, and used as a non-invasive method to diagnose and monitor disease. We propose to isolate circulating tumour DNA from the plasma of high-risk endometrial patients, and then use sequencing technology to find specific gene mutations. The presence or absence of plasma circulating tumour DNA may be used as a biomarker to determine if treatments are effective and if alternative patient-specific treatment is needed. This cutting edge genomics research has major implications for Canadian women's health, as it will be used to improve and develop much needed translational research for an often lethal uterine cancer.