Combining these results with the single-cell SNV results, we found that (1) SNVs occurred earlier in the premalignant stage, which might play an important role in tumor initiation (Fig. 5b); (2) CNVs were acquired later in a burst, which characterized the malignancy and promoted tumor formation and progression (Fig. 5b); and (3) metastatic tumors originate from PTs with increased frequency of co-occurrence of two SNV mutations (Arhgef11 and Plekha5) from 44 to 65% and CNVs within the same single cells, indicating the contribution of CNVs to the driving force for tumor metastasis (Fig. 5c). Here, ARHGEF11 is linked to neoplasm.