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Figure 3 shows the Venn diagram of overlapping genes in the lower preva lent histotypes. Due to the differences in sample size of each histotype, comparisons between overlapped genes were limited to genes found JAK3 阻害剤 only in the non serous tumors where the sample sizes are more comparable. A small number of overlapped amplified and deleted genes between clear cell and mucinous tumors were observed, none with endometrioid. This suggests that most of the CNA are specific to histotypes, adding to the mounting evidence of molecular differences between histotypes. Despite larger sample size in serous histotype, comparison of CNA found in the lower prevalent histotypes with ser ous is also of interest. Clear cell tumors had the highest number of common altered genes with serous tumors while endometrioid tumors had the lowest number of common altered genes, 3.

0% common altered genes with serous tumors only. There is also more overlap on amplifications than deletions. Consistency with other studies Three studies have reported copy number changes in EOC. These stud ies focused on global changes in EOC rather than histotype specific alterations. Nevertheless, histotype specific alterations from our study should overlap supplier LDE225 to some degree with these reported genes. We compiled a list of 551 significant genes reported in the 3 studies of which 545 genes were reported by either Haverty et al. or Gorringe et al. Eleven genes were commonly identified in at least 2 of the studies. In comparison, 39. 2% of genes were found in our study, indi cating that our approach can identify copy number altered genes.

We also compared our findings in serous tumors with TCGA high grade serous study where they reported LY2157299 TGF-beta 阻害剤 63 regions of gains and 50 regions of deletion. Based on overlapping of genes or genomic regions, 29 63 amplified and 27 50 deleted regions were also found in our study. Copy number alterations in known cancer genes 300 cancer genes were previously reported, of which 76 cancer genes were found within the altered regions. We found that copy number alterations of these cancer genes were specific to histotypes as well, e. g. TPM3 amplification in endometrioid tumors, JAK2 deletion in mucinous, RB1 deletion in both clear cell and serous tumors, TP53 and MAP2K4 deletion in mu cinous and serous tumors. ERBB2, a gene implicated in breast and EOC showed significant focal amplification in mucinous tumors but deletions in serous tumors.

Evalu ation of ERBB2 expression between mucinous and ser ous tumors in the 3 datasets showed the trend of over expression of ERBB2 in mucinous compared to serous. The focal amplification of ERBB2 has been observed in various studies, supporting our findings. Identification of candidate driver genes in EOC histotypes To identify candidate driver genes that might contribute to carcinogenesis of EOC, we looked for genes that showed association between copy number and gene ex pression. Table 1 summarized the alterations and potential cancer driver genes based on cytoband. Pathway analysis of potential driver genes in Table 1 showed top molecular functions of these genes to be involved with cell cycle, cellular development, growth and proliferation.