TY - JOUR
T1 - Genome-wide DNA methylation profiles in both precancerous conditions and clear cell renal cell carcinomas are correlated with malignant potential and patient outcome
AU - Arai, Eri
AU - Ushijima, Saori
AU - Fujimoto, Hiroyuki
AU - Hosoda, Fumie
AU - Shibata, Tatsuhiro
AU - Kondo, Tadashi
AU - Yokoi, Sana
AU - Imoto, Issei
AU - Inazawa, Johji
AU - Hirohashi, Setsuo
AU - Kanai, Yae
N1 - Funding Information:
Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan; Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan; New Energy and Industrial Technology Development Organization; Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation. Funding to pay the Open Access publication charges for this article was provided by a Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
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U2 - 10.1093/carcin/bgn268
DO - 10.1093/carcin/bgn268
M3 - Article
C2 - 19037089
AN - SCOPUS:60149106402
SN - 0143-3334
VL - 30
SP - 214
EP - 221
JO - Carcinogenesis
JF - Carcinogenesis
IS - 2
ER -
