Identification of Genes Preferentially Required for Growth of p53-Deficient Human Cancer Cells

We describe a synthetic interaction screen to identify genes preferentially required for proliferation of p53-deficient human cancer cells. An isogenic pair of p53+/+ and p53-/- human colorectal HCT116 cell lines was stably transduced with a short hairpin RNA (shRNA) library encoded by lentiviruses that integrate in the genomic DNA of the host. Comparison of the frequency of each type of integrated lentivirus in the 2 cell types at an early time point (40hrs) and after about 12 mitotic cycles (10days), reveals genes whose knockdown preferentially impaired growth of p53-/- or p53+/+ HCT116 cells. Keywords: Functional Genomics The region of the integrated lentiviruses is PCR amplified from genomic DNA of the two transduced cell populations at an early and a late time point.