Fig. 2: Two growth patterns are associated with two cNRT acquisition patterns.

a In vivo tumor growth curves of three p53CKO models were determined by serial MRI. In mice with multifocal masses, the fastest-growing tumor is shown. b Representative 3D-reconstruction of MRI images shows the single-mass Type 1 (upper panel) and multifocal-mass Type 2 (bottom panel) growth patterns. c Frequency of Type 1 and Type 2 growth patterns in three p53CKO models was determined by serial MRI. The single-mass Type 1 pattern was marked by black. The multifocal-mass Type 2 pattern was presented by three types: (1) no merge (red), (2) partial merge (red with diamonds), and (3) complete merge (could be misdiagnosed as Type 1, red with stripes). The percentage of cells from each tumor sample carrying a nonreciprocal translocation (NRT) (d) and the percentage of cells carrying the dominant NRT (the NRT with the highest frequency in a tumor sample) (e) were compared. Each dot represents a tumor sample. Data are presented as a dot plot with mean ± SEM. f Representative spectral karyotyping (SKY) images identify clonal NRT(s) (cNRTs, observed in over 50% of the metaphases analyzed in a given sample). Analysis of SKY images demonstrates that a sub-4N Type 1 tumor cell at end-stage contained only one copy of its cNRT (upper panel), while a sub-4N Type 2 tumor cell typically contained two copies of its cNRT (bottom panel). g Schematic illustration of a cNRT acquired in a cell with a 4N genome (cNRT4N, blue) or acquired in a cell with a 2N genome (cNRT2N, red). h The percentage of sub-4N tumors in Type 1 and Type 2 cases carrying cNRT4N(s) and/or cNRT2N(s) was shown. i Proposed tumor evolution patterns in Type 1 and Type 2 cases. Briefly, Type 1 tumors could only be traced back to a cNRT4N-bearing cell with a sub-4N genome (blue square), while Type 2 tumors could be traced back to a cNRT2N-bearing cell with a near-2N genome (red squares). Unpaired, two-tailed Student’s t test was used for statistical analysis in (d, e, h). ****p < 0.0001.