First, Pathway Studio identified multiple references supporting positive modulatory roles for AGER and TNF. Furthermore, TNF is a positive modulator of the cell death pathway known as necroptosis, which is negatively modulated by CASP8. 25-29 Since CASP8 is expressed in only 16% of neuroblastoma cell lines,30 it is possible that the H4 neuroblastoma cell line used in siRNA screen 2 was deficient in CASP8 or another negative modulator of necroptosis, rendering the H4 line susceptible to uncontrolled necroptosis.28 This evidence concerns the gene AGER and neuroblastoma.