Whole-exome sequencing (WES) of the PDOs (Fig. 4) revealed that PCRC-1 presented alterations in common CRC mutated genes, such as APC, KRAS and TP53. PCRC-2 contained alterations in APC, KRAS, FBXW7 and NOTCH1 genes, Fig. 4A. PCRC-3 had an inactivating mutation in MLH1 causing deficiency in MMR. The gene discussed is NOTCH1; the disease is colorectal carcinoma.