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DNA methylation status defines clinicopathological parameters including survival for patients with clear cell renal cell carcinoma (ccRCC)
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
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2016 (English)In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 37, no 8, 10219-10228 p.Article in journal (Refereed) Published
Abstract [en]

Epigenetic alterations in the methylome have been associated with tumor development and progression in renal cell carcinoma (RCC). In this study, 45 tumor samples, 12 tumor-free kidney cortex tissues, and 24 peripheral blood samples from patients with clear cell RCC (ccRCC) were analyzed by genome-wide promoter-directed methylation arrays and related to clinicopathological parameters. Unsupervised hierarchical clustering separated the tumors into two distinct methylation groups (clusters A and B), where cluster B had higher average methylation and increased number of hypermethylated CpG sites (CpGs). Furthermore, tumors in cluster B had, compared with cluster A, a larger tumor diameter (p = 0.033), a higher morphologic grade (p < 0.001), a higher tumor-node-metastasis (TNM) stage (p < 0.001), and a worse prognosis (p = 0.005). Higher TNM stage was correlated to an increase in average methylation level (p = 0.003) and number of hypermethylated CpGs (p = 0.003), whereas a number of hypomethylated CpGs were mainly unchanged. However, the predicted age of the tumors based on methylation profile did not correlate with TNM stage, morphological grade, or methylation cluster. Differently methylated (DM) genes (n = 840) in ccRCC samples compared with tumor-free kidney cortex samples were predominantly hypermethylated and a high proportion were identified as polycomb target genes. The DM genes were overrepresented by transcription factors, ligands, and receptors, indicating functional alterations of significance for ccRCC progression. To conclude, increased number of hypermethylated genes was associated with increased TNM stage of the tumors. DNA methylation classification of ccRCC tumor samples at diagnosis can serve as a clinically applicable prognostic marker in ccRCC.

Place, publisher, year, edition, pages
2016. Vol. 37, no 8, 10219-10228 p.
Keyword [en]
Clear cell renal cell carcinoma, DNA methylation, Survival, Predicted age, Polycomb target genes
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-126325DOI: 10.1007/s13277-016-4893-5ISI: 000382672900022PubMedID: 26831665OAI: oai:DiVA.org:umu-126325DiVA: diva2:1040307
Available from: 2016-10-27 Created: 2016-10-03 Last updated: 2016-10-27Bibliographically approved

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Evelönn, Emma AnderssonDegerman, SofieKöhn, LindaLandfors, MattiasLjungberg, BörjeRoos, Göran
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PathologyDepartment of Mathematics and Mathematical StatisticsUrology and Andrology
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