Genome-wide DNA methylation profiles in both precancerous conditions and clear cell renal cell carcinomas are correlated with malignant potential and patient outcome

Eri Arai, Saori Ushijima, Hiroyuki Fujimoto, Fumie Hosoda, Tatsuhiro Shibata, Tadashi Kondo, Sana Yokoi, Issei Imoto, Johji Inazawa, Setsuo Hirohashi, Yae Kanai

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Abstract

To clarify genome-wide DNA methylation profiles during multistage renal carcinogenesis, bacterial artificial chromosome array-based methylated CpG island amplification (BAMCA) was performed. Non-cancerous renal cortex tissue obtained from patients with clear cell renal cell carcinomas (RCCs) (N) was at the precancerous stage where DNA hypomethylation and DNA hypermethylation on multiple bacterial artificial chromosome (BAC) clones were observed. By unsupervised hierarchical clustering analysis based on BAMCA data for their N, 51 patients with clear cell RCCs were clustered into two subclasses, Clusters AN(n=46) and BN(n = 5). Clinicopathologically aggressive clear cell RCCs were accumulated in Cluster BN, and the overall survival rate of patients in Cluster BN was significantly lower than that of patients in Cluster AN. By unsupervised hierarchical clustering analysis based on BAMCA data for their RCCs, 51 patients were clustered into two subclasses, Clusters AT (n = 43) and BT(n = 8). Clinicopathologically aggressive clear cell RCCs were accumulated in Cluster BT, and the overall survival rate of patients in Cluster BT was significantly lower than that of patients in Cluster AT. Multivariate analysis revealed that belonging to Cluster BT was an independent predictor of recurrence. Cluster BN was completely included in Cluster BT, and the majority of the BAC clones that significantly discriminated Cluster BN from Cluster AN also discriminated Cluster BT from Cluster AT. In individual patients, DNA methylation status in N was basically inherited by the corresponding clear cell RCC. DNA methylation alterations in the precancerous stage may generate more malignant clear cell RCCs and determine patient outcome.

Original languageEnglish
Pages (from-to)214-221
Number of pages8
JournalCarcinogenesis
Volume30
Issue number2
DOIs
Publication statusPublished - 2009
Externally publishedYes

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Precancerous Conditions
DNA Methylation
Renal Cell Carcinoma
Genome
Bacterial Artificial Chromosomes
CpG Islands
Cluster Analysis
Survival Rate
Clone Cells
Kidney
DNA
Carcinogenesis
Multivariate Analysis

ASJC Scopus subject areas

  • Cancer Research

Cite this

Genome-wide DNA methylation profiles in both precancerous conditions and clear cell renal cell carcinomas are correlated with malignant potential and patient outcome. / Arai, Eri; Ushijima, Saori; Fujimoto, Hiroyuki; Hosoda, Fumie; Shibata, Tatsuhiro; Kondo, Tadashi; Yokoi, Sana; Imoto, Issei; Inazawa, Johji; Hirohashi, Setsuo; Kanai, Yae.

In: Carcinogenesis, Vol. 30, No. 2, 2009, p. 214-221.

Research output: Contribution to journalArticle

Arai, Eri ; Ushijima, Saori ; Fujimoto, Hiroyuki ; Hosoda, Fumie ; Shibata, Tatsuhiro ; Kondo, Tadashi ; Yokoi, Sana ; Imoto, Issei ; Inazawa, Johji ; Hirohashi, Setsuo ; Kanai, Yae. / Genome-wide DNA methylation profiles in both precancerous conditions and clear cell renal cell carcinomas are correlated with malignant potential and patient outcome. In: Carcinogenesis. 2009 ; Vol. 30, No. 2. pp. 214-221.
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