Table 1.
Discriminating Features Of The Five Major Histotypes Of Ovarian Carcinoma.
Figure 1.
Prediction of histotype was in part based on the COSP algorithm using 9 IHC markers [2].
(A–B) representative IHC from a typical high-grade serous ovarian carcinoma cell line, Kuramochi, and a clear cell carcinoma cell line, TOV21G. In addition to the 9-marker COSP panel, IHC for ARID1A (BAF250a) is also shown as a mutation surrogate. (C) TFF3 mRNA expression from 60 ovarian cancer samples (12 of each histotype). As noted previously high expression is most prevalent in MUC, followed by ENOCa and LGSC [2], [4]. Expression in our pilot cohort suggests the highest levels of TFF3 in MUC, which was significantly higher than all other groups (Tukey's adjusted p<0.01); no other pairwise comparisons had p<0.05. (D) TFF3 mRNA detected in ovarian cancer cell lines was used in place of an IHC score as the secreted TFF3 was considered a poor biomarker for cell culture conditions. Any cell line with measurable TFF3 mRNA above the NanoString detection threshold (see methods) was considered positive (score of 1 for use in the COSP algorithm).
Table 2.
Validation of the histotype of commonly used ovarian carcinoma cell lines using immunohistochemistry based prediction via COSP and mutational profiling.
Figure 2.
Genome-wide copy number profiles of bona-fide ovarian CCC cell lines.
A large range of copy number changes are seen including typical Chr8 gains and Chr17 gains surrounding the CCC biomarker HNF1B gene, see also Table 3.
Table 3.
Copy number changes across putative CCC oncogenes, tumor suppressors, and biomarkers.
Figure 3.
Genomic structure of CCC cell line JHOC-9. (A) 24 color FISH analysis suggested the presence of two dominant clones; one near-diploid and one near-tetraploid in the JHOC-9 CCC cell line.
A number of translocations and rearrangements can be seen in each representative clone. The complex karyotype of each dominant clone is noted below the corresponding 24-colour FISH results. Not all derivative chromosomes were identifiable resulting in a large number of ambiguous translocations and fragments (denoted by question marks in the karyotype notations). (B) Circos plot of RNAseq data and deFuse analysis depicting expressed genomic rearrangements in the JHOC-9 cell line. Translocations seen in the 24-color FISH profile are also visible as expressed transcripts including t(8;19) observed in both 2N and 4N dominant clones. No recurrent translocations were seen across our series (see also Table S3).