ENAGenomicsEUROPEAN RESEARCH INSTITUTE FOR THE BIOLOGY OF AGEING, UNIVERSITY OF GRONINGEN, UNIVERSITY MEDICAL CENTER GRONINGENhttps://www.ebi.ac.uk/ena/browser/view/PRJEB35930The PIDDosome is a multimeric protein complex that activates caspase-2 in response to supernumerary centrosomes. In polyploid hepatocytes, this pathway is activated to induce a p53-depenent cell cycle arrest. Thereby, the PIDDosome controls the upper limit of hepatic ploidy during development and regeneration. Since caspase-2 has been suggested to delete aneuploid cancer cells [1, 2], we employed single cell sequencing techniques to test whether caspase-2 itself or caspase-2 mediated p53 activation are involved in this process during hepatocarcinogenesis. Murine liver tumors were induced using diethylnitrosamine (DEN, 25mg /kg, i.p.) injected at the age of 15 days and analyzed 10 months later. Nuclei of tumor tissue of ten wt or caspase-2 deficient mice were isolated and per tumor 30 diploid and tetraploid cells were sorted and sequenced in bulk. Our data suggest that tetraploid tumor cells tend to have a higher degree of aneuploidy which is independent of caspase-2 as both wt and caspase-2 deficient tumors showed a similar degree of copy number variation. 1) López-García, C., Sansregret, L., Domingo, E., McGranahan, N., Hobor, S., Birkbak, N. J., … Swanton, C. (2017). BCL9L Dysfunction Impairs Caspase-2 Expression Permitting Aneuploidy Tolerance in Colorectal Cancer. Cancer Cell, 31(1), 79–93. https://doi.org/10.1016/j.ccell.2016.11.0012) Dawar, S., Lim, Y., Puccini, J., White, M., Thomas, P., Bouchier-Hayes, L., … Kumar, S. (2017). Caspase-2-mediated cell death is required for deleting aneuploid cells. Oncogene, 36(19), 2704–2714. https://doi.org/10.1038/onc.2016.423ENANedd2, Aneuploids, Carcinoma, Procaspase-2, Controlling, preventive therapy, Liver, Caspase-2, Cell Carcinoma, Liver Cell, adult hepatoma, Hepatomas, Liver Cell Carcinoma, Cell, prevention, ICH1, Cell Carcinomas, Aneuploidies, HCC, chromosome number anomaly, Liver Cell Carcinomas, Hepatocellular Carcinoma., Caspase 2 Subunit p12, Adult Liver Cancer, Adult Liver, ICH-1, prevention and control, Aneuploid Cell, Carcinomas, reference sample, Adult Liver Cancers, Hepatocellular carcinoma, Liver Cancer, Aneuploid, Hepatoma, prophylaxis, Pro Caspase 2, Caspase 2 Subunit p13, adult primary hepatocellular carcinoma, Liver Cancers, Caspase 2 Subunit p18, Cancers, Adult, preventive measures, Aneuploid Cells, ICH 1 Protease, Procaspase 2, control, Pro-Caspase-2, Cells, NEDD2, Hepatocellular, ICH-1 Protease, Hepatocellular Carcinomas, Controlled, CancerNedd2, Aneuploids, Carcinoma, Procaspase-2, Controlling, preventive therapy, Liver, Caspase-2, Cell Carcinoma, Liver Cell, adult hepatoma, Hepatomas, Liver Cell Carcinoma, Cell, prevention, ICH1, Cell Carcinomas, Aneuploidies, HCC, chromosome number anomaly, Liver Cell Carcinomas, Hepatocellular Carcinoma., Caspase 2 Subunit p12, Adult Liver Cancer, Adult Liver, ICH-1, prevention and control, Aneuploid Cell, Carcinomas, reference sample, Adult Liver Cancers, Hepatocellular carcinoma, Liver Cancer, Aneuploid, Hepatoma, prophylaxis, Pro Caspase 2, Caspase 2 Subunit p13, adult primary hepatocellular carcinoma, Liver Cancers, Caspase 2 Subunit p18, Cancers, Adult, preventive measures, Aneuploid Cells, ICH 1 Protease, Procaspase 2, control, Pro-Caspase-2, Cells, NEDD2, Hepatocellular, ICH-1 Protease, Hepatocellular Carcinomas, Controlled, CancerfalseCaspase-2 and the PIDDosome do not control aneuploidy in hepatocellular carcinomaCaspase-2 and the PIDDosome do not control aneuploidy in hepatocellular carcinoma2019-12-202021-01-05PRJEB35930