Figure 1.
Genomic and epigenetic features of tumor suppressors and oncogenes.
Copy number variation is the base genomic feature for our identification of tumor suppressor and oncogenic gene properties in ovarian cancer. An oncogene can be overexpressed under amplified copy number and low methylation, while hypermethylation can be used for regulating expression in a gene amplified state. Similarly, decreased tumor suppressor expression can be the result of partial copy number loss with hypermethylation. Tumor suppressors may also possibly be regulated via hypomethylation in a copy number deleted stated. Our analysis is modeled for such properties and first examines the CNV per gene and then attributes epigenetic alteration for each copy number aberration with gene expression.
Figure 2.
Amplification and deletion breakpoint variability among ROMA segments.
Breakpoint positions of copy number variability (deletions depicted in blue, amplifications depicted in red) in 22 chromosomes are shown as determined from ROMA generated segmentation data. The initial altering deletion or amplification genomic position is depicted from all 42 ovarian tumor cancer samples.
Figure 3.
MOMA methylation in ovarian cancer tumors.
The tumor:normal ratio percentage for MOMA methylation per gene from 42 ovarian cancer tumor samples and 7 tissue normal samples is outlined per chromosome. For each sample the mean methylation value is calculated from the maximum MOMA value per probe that incorporates the gene promoter region. MOMA methylation data covered 11,978 gene promoter regions. Prominent hypermethylation (red) and hypomethylation (green) genes are labeled and provided in Table S2.
Table 1.
Chromosomal deletions and amplifications in ovarian cancer tumors*.
Figure 4.
Distribution of gene expression per copy number variation from ovarian cancer tumor cells.
As gene copy number variation increases from deletion to amplification the mean gene expression also increases in both the MSKCC (blue line) and TCGA (green line) data sets.
Table 2.
Selected ovarian cancer genes captured by Wilcoxon rank test based on copy number variation and expression data*.
Figure 5.
Oncogenic and tumor suppressor features in ovarian cancer.
We isolated genes (all points) with extreme copy number variation from the TCGA (A and C) and MSKCC (B and D) data sets. Methylation and tumor to normal expression ratio was then compared for genes at low CNV (A and B) and high CNV (C and D). Genes with oncogenic features (blue ovals; high expression and low methylation) and tumor suppressor features (red ovals; low expression and high methylation) were identified (Table 3).
Figure 6.
Ranking of significantly expressed and methylated genes with copy number variation.
Predicted MSKCC data set genes (green circle) with changes in methylation and expression are overlayed a genome wide stair-plot of ROMA probe sample frequencies per deletion and amplification (blue line). Each predicted gene is percentile ranked according to its FDR p-values (<0.05) between normal and tumor samples.
Table 3.
Copy number variation derived methylation and expression of tumor suppressors and oncogenes in ovarian cancer*.