Figure 3

Acute upregulation of FOXM1B induces genomic instability in primary NHEK. (A) Early passage (P1) primary NHEK were either mock transduced, EGFP or FOXM1B transduced, left to grow for 4 days and gDNA was harvested for SNP array analysis. LOH and CNV data were obtained by comparing test samples (EGFP or FOXM1B) with reference genome (mock transduced NHEK). (B) CNV (Log 2 ratio, red dots), LOH (blue lines) and LOH likelihood (grey lines) plots for EGFP or FOXM1B expressing cells. LOH likelihood was calculated based on Affymetrix GTYPE algorithm [15, 66]. (C) Three normal healthy primary keratinocytes (NHEK#1-3) SNP copy number analysis showing CNV (ploidy number N < 2) and gains (N > 2) in EGFP and FOXM1B overexpressing NHEK, respectively. (D) Average fold-increase in genomic instability of the 3 normal primary NHEK cells in C. *(P < 0.05) indicates significant increase in FOXM1B-induced genomic instability (E) FOXM1B-induced CNV (total SNP number undergoing CNV as indicated above each bar) showed gradual accumulation during a short-term primary NHEK culture (3 passages, P1, P2 and P3). (F) FOXM1B, but not EGFP, enhances LOH and CNV formation in N/TERT cells that survived UVB insult. Ideogram of chromosome 6 and 7 showing regions of CNV and LOH as indicated.