POLD1 and neoplasm: While the analysis of MSI-H status or inactivation of POLE or POLD1 genes relies on relatively straightforward laboratory tests, the determination of tumor mutation burden in, e.g., lung cancers or melanomas, is more complicated: it is based on the whole exome sequencing, deals with continuous variable and does not have yet established thresholds for clinical decisions (Rizvi et al., 2015; Van Allen et al., 2015).