A meta-analysis to identify novel candidate genes in the development of hepatocellular carcinoma
JOURNAL OF HEPATOLOGY(2022)
Abstract
50% of the mitotic events in Mcl-1 Dhep livers were aberrant (Fig. B), with abnormal chromosome segregation.WES of Mcl-1 Dhep tumors of 12 months old mice showed a mean CIN of 33.8% (Fig. C).Following PHx, liver weight to body weight ratios were similar in Mcl-1 Dhep and WT mice during liver regeneration, while Mcl-1 Dhep livers were smaller prior to PHx (Fig. E).Mcl-1 Dhep hepatocytes progressed faster through G2/M.At the proliferative peak, abnormal mitotic figures were observed with similar frequency in Mcl-1 Dhep and WT livers (Fig. F).After regeneration, the ploidy profile was comparable in WT and Mcl-1 Dhep livers (Fig. G).Both WT and Mcl-1 Dhep livers harbored very low level of SNVs and indels.Conclusion: In 2 months old mice, hepatocytes lacking Mcl-1 exhibit nuclear polyploidy, mitotic errors and abnormal chromosome segregation leading to CIN. Surprisingly, similar rates of aberrant mitosis were observed in WT and Mcl-1 Dhep livers upon hyperproliferation.And after hyperproliferation, WT and Mcl-1 Dhep livers exhibited similar levels of abnormal nuclear morphology, of low mutational burden and of high proportion of polyploid nuclei.
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Key words
hepatocellular carcinoma,novel candidate genes,meta-analysis
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