In other words, while the computational approaches can provide potential candid

Endometrioid and serous tend to harbor more copy num ber alterations, with more broad regions of alterations in volving the p or q arm. The genomics landscape for clear cell and mucinous tumors appeared Janus キナーゼ 阻害剤 different from the other histotypes, with lesser broad regions of alterations and in lower frequency. To assess the significance of copy number altered regions, we used a 2 pronged approach using merged and individual datasets. Figure 2 shows significant copy number altered regions in the histotypes. Broad 3p amplification and 8p deletion were observed in serous tumors, 8q amplifications in clear cell and serous tumors, 17p de letions in mucinous and serous tumors, and chr20 amplifi cations in serous tumors. The nature of the alterations also differs, e. g. focal versus broad alterations.

For example in 3q, serous tumors showed broader amplifications in the region of 3q13. 31 29 while focal amplification was observed for clear cell tumors at 3q26. 2 26. 32. This is interesting as 価格 LDE225 it has been reported that overlapping broad and focal aberrations can have distinct functional conse quences. In other chromosomes, alterations were spe cific to histotypes as well, such as 9p21 focal deletions in mucinous histotype, reportedly harboring homozygous deletions in EOC. There are regions that displayed opposite trend in alterations between histotypes. One par ticular region, 8p23. 1, showed amplification in clear cell but deletion in serous tumors. Another region which showed opposite trend in alteration was 17q12 which har bor the oncogene ERBB2, the gene was significantly ampli fied in mucinous but deleted in serous tumors.

Excluding borderline cases, 28. 6% mucinous samples had amplifications and 15. 2% LY2157299 700874-72-2 of serous tumors had deletions of ERBB2. 1 5 mucinous borderline also showed ERBB2 amplification. It should be of note that although ERBB2 was found significantly deleted in serous tumors, 5 99 of serous samples harbored the amplification, close to the 3% reported by TCGA for high grade serous. No ERBB2 deletion was observed in the mucinous samples. As serous tumors have a comparatively larger sample size than the other histotypes, we would expect more significant regions for this histotype. Nevertheless, using stringent criteria, we were able to identify some sig nificant CNA for the lower prevalent tumors.

To quantify genes that were altered in each histotype, we mapped genes to regions that were identified in each histotype. 6375 unique genes were found to be altered, 2682 amplifications and 3712 deletions. 91% of genes were amplified and 97. 1% deleted in serous tumors, 19. 1% amplified and 1. 5% deleted in clear cell, 14. 3% amplified in endometrioid, and 0. 5% amp lified and 11. 5% deleted in mucinous. A total of 5360 genes were specific to each histotype, 5011 in serous tumors, 193 in endome trioid tumors, 79 in clear cell tumors, and 77 in mucinous tumors. Within each histotype, the type of alterations varied. Clear cell tumors had more amplified genes than deleted genes, while mucinous and serous tumors had more deleted genes than amplified genes. Only amplified genes were found in endometrioid tumors.