Molecular Classification of Epithelial Ovarian Cancer Based on Methylation Profiling: Evidence for Survival Heterogeneity

Ovarian cancer is a heterogeneous disease that can be divided into multiple subtypes with variable etiology, pathogenesis, and prognosis. We analyzed DNA methylation profiling data to identify biologic subgroups of ovarian cancer and study their relationship with histologic subtypes, copy number var...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Clinical cancer research Ročník 25; číslo 19; s. 5937
Hlavní autoři: Bodelon, Clara, Killian, J Keith, Sampson, Joshua N, Anderson, William F, Matsuno, Rayna, Brinton, Louise A, Lissowska, Jolanta, Anglesio, Michael S, Bowtell, David D L, Doherty, Jennifer A, Ramus, Susan J, Talhouk, Aline, Sherman, Mark E, Wentzensen, Nicolas
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.10.2019
Témata:
Carcinoma, Ovarian Epithelial
DNA Copy Number Variations
Female
Gene Expression Regulation, Neoplastic
Humans
Methylation
Ovarian Neoplasms - genetics
ISSN:1557-3265, 1557-3265
On-line přístup:Zjistit podrobnosti o přístupu
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí:Ovarian cancer is a heterogeneous disease that can be divided into multiple subtypes with variable etiology, pathogenesis, and prognosis. We analyzed DNA methylation profiling data to identify biologic subgroups of ovarian cancer and study their relationship with histologic subtypes, copy number variation, RNA expression data, and outcomes. A total of 162 paraffin-embedded ovarian epithelial tumor tissues, including the five major epithelial ovarian tumor subtypes (high- and low-grade serous, endometrioid, mucinous, and clear cell) and tumors of low malignant potential were selected from two different sources: The Polish Ovarian Cancer study, and the Surveillance, Epidemiology, and End Results Residual Tissue Repository (SEER RTR). Analyses were restricted to Caucasian women. Methylation profiling was conducted using the Illumina 450K methylation array. For 45 tumors array copy number data were available. NanoString gene expression data for 39 genes were available for 61 high-grade serous carcinomas (HGSC). Consensus nonnegative matrix factorization clustering of the 1,000 most variable CpG sites showed four major clusters among all epithelial ovarian cancers. We observed statistically significant differences in survival (log-rank test, = 9.1 × 10 ) and genomic instability across these clusters. Within HGSC, clustering showed three subgroups with survival differences (log-rank test, = 0.002). Comparing models with and without methylation subgroups in addition to previously identified gene expression subtypes suggested that the methylation subgroups added significant survival information ( = 0.007). DNA methylation profiling of ovarian cancer identified novel molecular subgroups that had significant survival difference and provided insights into the molecular underpinnings of ovarian cancer. .
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
ObjectType-Commentary-3
content type line 23
ISSN:1557-3265
1557-3265
DOI:10.1158/1078-0432.CCR-18-3720