Table 1.
TP53 mutation spectrum and global chromosomal anomalies assessed by SNP array analyses in 87 HGSC verified cases.
Figure 1.
TP53 gene expression, protein expression and Kaplan-Meier survival curve analyses in HGSC cases.
Ziplex® custom array-derived TP53 gene expression data for 76 of the 87 HGSC cases, grouped according to TP53 mutation type (A). The mean TP53 gene expression values for missense (n = 45), frameshift (n = 9), splice (n = 7), nonsense (n = 6), in-frame insertion (n = 1) and mutation-negative (n = 8) HGSC cases are 232.2, 67.6, 70.1, 46.6, 148.9, and 114.5, respectively, as indicated by arrows. Immunohistochemistry analysis of 76 HGSC cores, arrayed on a tissue microarray, grouped according to TP53 mutation type (B). Positive p53 immunoreactivity was observed for 42/45 missense, 1/9 frameshift, 0/7 splice, 0/6 nonsense, 1/1 in-frame insertion, and 3/8 mutation-negative HGSC cases. Kaplan-Meier survival curve analysis of TP53 mutation-positive HGSC cases for overall survival, in months, of patients positive for p53 staining (n = 44) compared to patients negative for p53 staining (n = 24) (C). Kaplan-Meier survival curve analysis of TP53 mutation-positive HGSC cases for disease-free interval, in months, of patients positive for p53 staining (n = 44) compared to patients negative for p53 staining (n = 24) (D). Indicated p-values were derived from Mantel-Cox, log-rank tests.
Figure 2.
Chromosomal anomalies and breaks across the genome of TP53 mutation-positive HGSC cases.
Percentage of the 79 TP53 mutation-positive HGSCs with chromosomal anomalies, including copy number alteration and allelic imbalance, and breaks occurring per chromosome arm, as inferred by reviewing image files created by the Genome Viewer module in BeadStudio Data Analysis software v2.2.22. The chromosome arms are arranged according to their size in megabases, left to right from smallest to largest.
Figure 3.
Global regions of gain and loss in TP53 mutation-positive HGSC cases.
Global regions of gain and loss in the 79 TP53 mutation-positive HGSC cases, as determined by GenoCNA analyses (A). Regions of gain and loss occurring in >50% of the 79 HGSC cases are indicated by green arrowheads. Regions of gain and loss occurring in >50% of the TCGA samples [8] and in >39% of the AOCS samples [9] are indicated by solid and dashed arrows, respectively (red colour indicates gain, blue colour indicates loss). Global regions of gain and loss in the 44 HGSC cases expressing p53 mutant protein (B). Global regions of gain and loss in the 24 p53 protein null HGSCs (C). Regions found to be significantly gained in the cases expressing p53 mutant protein as compared to the p53 protein null cases by GenoCNA analyses include 1q, 8q and 12p, and are indicated by purple arrows.
Figure 4.
Chromosome 17 copy number alterations in TP53 mutation-positive HGSC cases.
GenoCNA analysis of Chromosome 17 copy number alterations in the 79 TP53 mutation-positive HGSC cases. The genomic loci of the genes TP53, NF1, and BRCA1 are indicated with arrows. CN, copy number; LOH, loss of heterozygosity.
Table 2.
Figure 5.
GenoCNA analysis comparing HGSC cases based on p53 immunoreactivity.
GenoCNA analysis comparing the mean copy number, on a per SNP basis, of the 44 samples expressing p53 mutant protein to that of the 24 p53 protein null HGSC cases for chromosomes 1 (A), 8 (B) and 12 (C), which contain regions significantly gained in the HGSC cases expressing p53 mutant protein as compared to the p53 protein null HGSC cases (see Figure 3B, C). Points on the plot represent –log10 of p-values from t-tests comparing the means in the two groups. Blue bars indicate regions of significant gain.