The non-random pairing of dissimilar APC mutations in tumors {e.g., protein truncation near the mutation cluster region (MCR) with allelic deletion or methylation}, coupled with functional studies of mutant Apc proteins [35], [36], has suggested that the cell must retain some ability to regulate Wnt/β-catenin signaling during tumor progression – the so-called “just right” hypothesis [37]. The gene discussed is APC; the disease is neoplasm.