Identification and Analysis of a New Tumor and Metastasis Suppressor Gene, RASAL2

Abstract

RAS is one of the most commonly mutated genes in human cancer; its aberrant activation drives tumor cell proliferation and survival. However, RAS mutations are rare in some cancers, including breast cancer, even though the Ras pathway is hyperactivated, suggesting that alternative mechanisms deregulate Ras signaling in these settings. The RasGAPs are negative regulators of Ras and, as such, are poised to function as tumor suppressors whose loss might contribute to Ras pathway hyperactivation in cancer. However, the RasGAPs remain an understudied family of genes whose role in cancer has not been fully explored. In this Dissertation I identify a previously uncharacterized RasGAP, RASAL2, as the newest tumor suppressor in this gene family.