In this study, we applied RNA sequencing, array comparative genomic hybridization (aCGH) and multicolor fluorescence in situ hybridization (mFISH) to analyze HCT116 p53 +/+ colon cancer cells and its drug-resistant subline with p53 deletion, HCT116 p53 −/−, to characterize genes, pathways, protein networks and chromosomal aberrations responsible for drug resistance in the HCT116 p53 −/− cell line. This evidence concerns the gene TP53 and colonic neoplasm.