This dissertation explores the importance of understanding the genetic mechanisms that lead to cancer. Specifically, in Chapter 2 succinate dehydrogenase subunit A variants of unknown significance are categorized based on how they affect succinate dehydrogenase complex function and therefore whether or not they predispose patients to succinate dehydrogenase-deficient cancer. Chapter 3 works to identify novel mechanisms of succinate dehydrogenase-deficiency in tumors with an unknown molecular classification. Finally, Chapter 4 reviews the genetic landscape of gastrointestinal stromal tumors and how it can be used to optimize clinical treatment. The overarching goal of this project is to establish a relationship between a patient’s genetic abnormality and the cancer it will initiate in order to guide clinical practice.