Steckel2012

Determination of synthetic lethal interactions in KRAS oncogene-dependent cancer cells reveals novel therapeutic targeting strategies.

• Steckel M, et al. Cell Res. 2012 Aug;22(8):1227-45

HCT-116 human colon cancer cells and the isogenic derivative, HKE-3, in which the activated, but not the normal, KRAS allele has been removed by homologous recombination a Delta-Z-score cut-off value of 3.3 was selected to generate a primary hit list of 89 genes (∼ 1.2% of the total number of genes screened) KRAS itself was placed ninth in this ΔZ-score ranking list, scoring very highly in HCT-116 and weakly in HKE-3 cells and thereby serving as an important internal control (Supplementary information, Table S1). Of the remaining 88 genes, 18 with a Z-score in excess of 2.0 in the HKE-3 cell line alone were eliminated from further analysis, following the reasoning that high levels of apoptosis resulting from siRNA-mediated silencing of these genes would likely constitute an undesirably strong cytotoxic effect in wild-type KRAS cells (Supplementary information, Figure S2B and S2C). Thus, our starting list for further validation comprised 70 candidate genes. 6159 lines in Harnessing Supp. Parse strategy delta_zscore >= 3.3 reveals 89 candidates (correct) if we remove kras and genes with HKE3_zscore > 2, we get to 70 genes (correct) This does not match with the Harnessing paper, which reports 80 SL genes. We will stick with the results of the initial screen, i.e., 70 genes, and count the rest as negatives.