NOTCH2 and neoplasm: The analysis of the 956 tumor samples that were contained in these data sets showed 42 mutations in NOTCH1, NOTCH2, or NOTCH3 clustered in the heterodimerization or in the PEST domain (a negative regulatory domain that is responsible for the degradation of the active Notch Intracellular Domain, NICD); furthermore, five additional patients displayed other alterations, such as large deletions, disrupting the PEST domain [383].