"Characterization of tumor evolution by functional clonality and phylogenetics in hepatocellular carcinoma"
Hepatocellular carcinoma (HCC) is a molecularly heterogeneous solid malignancy, and its fitness may be shaped by how its tumor cells evolve. However, ability to monitor tumor cell evolution is hampered by the presence of numerous passenger mutations that do not provide any biological consequences. Here, we developed a strategy to determine the tumor clonality of three independent HCC cohorts from 524 patients with diverse etiologies and race/ethnicity by utilizing somatic mutations in cancer driver genes. We identified two main types of tumor evolution, i.e., linear, and non-linear models where non-linear type could be further divide into shallow branching and deep branching. We found that linear evolving HCC is less aggressive than other types. GTF2IRD2B mutations were enriched in HCC with linear evolution while TP53 mutations were the most frequent genetic alterations in HCC with shallow branching and deep branching models. In addition, myeloid cells were more frequently associated with HCC`s non-linear evolution while lymphoid cells were more frequently associated with HCC`s linear evolution. These results suggest that tumor cells and their microenvironment shape the tumor evolution process.
Additional authors: Eric Slud, University of Maryland; Doron Levy, University of Maryland; Xin Wei Wang, National Institutes of Health.