DNA methylation profiles of ovarian clear cell carcinoma Journal Article
| Authors: | Cunningham, J. M.; Winham, S. J.; Wang, C.; Weiglt, B.; Fu, Z.; Armasu, S. M.; McCauley, B. M.; Brand, A. H.; Chiew, Y. E.; Elishaev, E.; Gourley, C.; Kennedy, C. J.; Laslavic, A.; Lester, J.; Piskorz, A.; Sekowska, M.; Brenton, J. D.; Churchman, M.; DeFazio, A.; Drapkin, R.; Elias, K. M.; Huntsman, D. G.; Karlan, B. Y.; Köbel, M.; Konner, J.; Lawrenson, K.; Papaemmanuil, E.; Bolton, K. L.; Modugno, F.; Goode, E. L. |
| Article Title: | DNA methylation profiles of ovarian clear cell carcinoma |
| Abstract: | Background: Ovarian clear cell carcinoma (OCCC) is a rare ovarian cancer histotype that tends to be resistant to standard platinum-based chemotherapeutics. We sought to better understand the role of DNA methylation in clinical and biological subclassification of OCCC. Methods: We interrogated genome-wide methylation using DNA from fresh frozen tumors from 271 cases, applied nonsmooth nonnegative matrix factorization (nsNMF) clustering, and evaluated clinical associations and biological pathways. Results: Two approximately equally sized clusters that associated with several clinical features were identified. Compared with Cluster 2 (N=137), Cluster 1 cases (N=134) presented at a more advanced stage, were less likely to be of Asian ancestry, and tended to have poorer outcomes including macroscopic residual disease following primary debulking surgery (P < 0.10). Subset analyses of targeted tumor sequencing and IHC data revealed that Cluster 1 tumors showed TP53 mutation and abnormal p53 expression, and Cluster 2 tumors showed aneuploidy and ARID1A/PIK3CA mutation (P < 0.05). Cluster-defining CpGs included 1,388 CpGs residing within 200 bp of the transcription start sites of 977 genes; 38% of these genes (N = 369 genes) were differentially expressed across cluster in transcriptomic subset analysis (P < 10-4). Differentially expressed genes were enriched for six immune-related pathways, including IFNα and IFNg responses (P < 10-6). Conclusions: DNA methylation clusters in OCCC correlate with disease features and gene expression patterns among immune pathways. © 2022 American Association for Cancer Research Inc.. All rights reserved. |
| Journal Title: | Cancer Epidemiology Biomarkers and Prevention |
| Volume: | 31 |
| Issue: | 1 |
| ISSN: | 1055-9965 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2022-01-01 |
| Start Page: | 132 |
| End Page: | 141 |
| Language: | English |
| DOI: | 10.1158/1055-9965.Epi-21-0677 |
| PUBMED: | 34697060 |
| PROVIDER: | scopus |
| PMCID: | PMC8755592 |
| DOI/URL: | |
| Notes: | Article -- MSK author Britta Weigelt's last name is misspelled on the original publication -- Export Date: 1 February 2022 -- Source: Scopus |
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