SPRED1 and in situ carcinoma: Interestingly, Spred1 (whose product also acts as negative regulator of the Ras pathway [68] and is a recently discovered melanoma tumor suppressor [69]) ranked within the top 10 CIS and exhibited a disruptive piggyBac insertional pattern, suggesting Spred1 acts as a novel tumor suppressor in glioma (Fig. 4c).