Genetic clustering of clear cell renal cell carcinoma based on array-comparative genomic hybridization: Its association with DNA methylation alteration and patient outcome

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

研究成果: Article

39 引用 (Scopus)

抄録

Purpose: The aim of this study was to clarify genetic and epigenetic alterations occurring during renal carcinogenesis. Experimental Design: Copy number alterations were examined by array-based comparative genomic hybridization analysis using an array harboring 4,361 bacterial artificial chromosome clones, and DNA methylation alterations on CpG islands of the p16, human MutL homologue 1, von Hippel-Lindau,and thrombospondin 1 genes and the methylated in tumor (MINT-1, MINT-2, MINT-12, MINT-25, and MINT-31) clones were examined in 51 clear cell renal cell carcinomas (RCC). Results: By unsupervised hierarchical clustering analysis based on copy number alterations, clear cell RCCs were clustered into the two subclasses, clusters A (n =34) andB(n = 17). Copy number alterations were accumulated in cluster B. Loss of chromosome 3p and gain of 5q and 7 were frequent in both clusters A and B, whereas loss of 1p, 4, 9, 13q, and 14q was frequent only in cluster B. The average number of methylated CpG islands in cluster B was significantly higher than those in cluster A. Clear cell RCCs showing higher histologic grades, vascular involvement, renal vein tumor thrombi, and higher pathologic stages were accumulated in cluster B. The recurrence-free and overall survival rates of patients in cluster B were significantly lower than those of patients in cluster A. Multivariate analysis revealed that genetic clustering was a predictor of recurrence-free survival and was independent of histologic grade and pathologic stage. Conclusions: This genetic clustering of clear cell RCC is significantly associated with regional DNA hypermethylation and may become a prognostic indicator for patients with RCC.

元の言語English
ページ(範囲)5531-5539
ページ数9
ジャーナルClinical Cancer Research
14
発行部数17
DOI
出版物ステータスPublished - 2008 9 1
外部発表Yes

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Comparative Genomic Hybridization
DNA Methylation
Renal Cell Carcinoma
Cluster Analysis
CpG Islands
Clone Cells
Chromosomes, Human, 4-5
Thrombospondin 1
Bacterial Artificial Chromosomes
Recurrence
Renal Veins
Epigenomics
Blood Vessels
Neoplasms
Carcinogenesis
Thrombosis
Research Design
Multivariate Analysis
Survival Rate
Kidney

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

これを引用

Genetic clustering of clear cell renal cell carcinoma based on array-comparative genomic hybridization : Its association with DNA methylation alteration and patient outcome. / Arai, Eri; Ushijima, Saori; Tsuda, Hitoshi; Fujimoto, Hiroyuki; Hosoda, Fumie; Shibata, Tatsuhiro; Kondo, Tadashi; Imoto, Issei; Inazawa, Johji; Hirohashi, Setsuo; Kanai, Yae.

:: Clinical Cancer Research, 巻 14, 番号 17, 01.09.2008, p. 5531-5539.

研究成果: Article

Arai, Eri ; Ushijima, Saori ; Tsuda, Hitoshi ; Fujimoto, Hiroyuki ; Hosoda, Fumie ; Shibata, Tatsuhiro ; Kondo, Tadashi ; Imoto, Issei ; Inazawa, Johji ; Hirohashi, Setsuo ; Kanai, Yae. / Genetic clustering of clear cell renal cell carcinoma based on array-comparative genomic hybridization : Its association with DNA methylation alteration and patient outcome. :: Clinical Cancer Research. 2008 ; 巻 14, 番号 17. pp. 5531-5539.
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abstract = "Purpose: The aim of this study was to clarify genetic and epigenetic alterations occurring during renal carcinogenesis. Experimental Design: Copy number alterations were examined by array-based comparative genomic hybridization analysis using an array harboring 4,361 bacterial artificial chromosome clones, and DNA methylation alterations on CpG islands of the p16, human MutL homologue 1, von Hippel-Lindau,and thrombospondin 1 genes and the methylated in tumor (MINT-1, MINT-2, MINT-12, MINT-25, and MINT-31) clones were examined in 51 clear cell renal cell carcinomas (RCC). Results: By unsupervised hierarchical clustering analysis based on copy number alterations, clear cell RCCs were clustered into the two subclasses, clusters A (n =34) andB(n = 17). Copy number alterations were accumulated in cluster B. Loss of chromosome 3p and gain of 5q and 7 were frequent in both clusters A and B, whereas loss of 1p, 4, 9, 13q, and 14q was frequent only in cluster B. The average number of methylated CpG islands in cluster B was significantly higher than those in cluster A. Clear cell RCCs showing higher histologic grades, vascular involvement, renal vein tumor thrombi, and higher pathologic stages were accumulated in cluster B. The recurrence-free and overall survival rates of patients in cluster B were significantly lower than those of patients in cluster A. Multivariate analysis revealed that genetic clustering was a predictor of recurrence-free survival and was independent of histologic grade and pathologic stage. Conclusions: This genetic clustering of clear cell RCC is significantly associated with regional DNA hypermethylation and may become a prognostic indicator for patients with RCC.",
author = "Eri Arai and Saori Ushijima and Hitoshi Tsuda and Hiroyuki Fujimoto and Fumie Hosoda and Tatsuhiro Shibata and Tadashi Kondo and Issei Imoto and Johji Inazawa and Setsuo Hirohashi and Yae Kanai",
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TY - JOUR

T1 - Genetic clustering of clear cell renal cell carcinoma based on array-comparative genomic hybridization

T2 - Its association with DNA methylation alteration and patient outcome

AU - Arai, Eri

AU - Ushijima, Saori

AU - Tsuda, Hitoshi

AU - Fujimoto, Hiroyuki

AU - Hosoda, Fumie

AU - Shibata, Tatsuhiro

AU - Kondo, Tadashi

AU - Imoto, Issei

AU - Inazawa, Johji

AU - Hirohashi, Setsuo

AU - Kanai, Yae

PY - 2008/9/1

Y1 - 2008/9/1

N2 - Purpose: The aim of this study was to clarify genetic and epigenetic alterations occurring during renal carcinogenesis. Experimental Design: Copy number alterations were examined by array-based comparative genomic hybridization analysis using an array harboring 4,361 bacterial artificial chromosome clones, and DNA methylation alterations on CpG islands of the p16, human MutL homologue 1, von Hippel-Lindau,and thrombospondin 1 genes and the methylated in tumor (MINT-1, MINT-2, MINT-12, MINT-25, and MINT-31) clones were examined in 51 clear cell renal cell carcinomas (RCC). Results: By unsupervised hierarchical clustering analysis based on copy number alterations, clear cell RCCs were clustered into the two subclasses, clusters A (n =34) andB(n = 17). Copy number alterations were accumulated in cluster B. Loss of chromosome 3p and gain of 5q and 7 were frequent in both clusters A and B, whereas loss of 1p, 4, 9, 13q, and 14q was frequent only in cluster B. The average number of methylated CpG islands in cluster B was significantly higher than those in cluster A. Clear cell RCCs showing higher histologic grades, vascular involvement, renal vein tumor thrombi, and higher pathologic stages were accumulated in cluster B. The recurrence-free and overall survival rates of patients in cluster B were significantly lower than those of patients in cluster A. Multivariate analysis revealed that genetic clustering was a predictor of recurrence-free survival and was independent of histologic grade and pathologic stage. Conclusions: This genetic clustering of clear cell RCC is significantly associated with regional DNA hypermethylation and may become a prognostic indicator for patients with RCC.

AB - Purpose: The aim of this study was to clarify genetic and epigenetic alterations occurring during renal carcinogenesis. Experimental Design: Copy number alterations were examined by array-based comparative genomic hybridization analysis using an array harboring 4,361 bacterial artificial chromosome clones, and DNA methylation alterations on CpG islands of the p16, human MutL homologue 1, von Hippel-Lindau,and thrombospondin 1 genes and the methylated in tumor (MINT-1, MINT-2, MINT-12, MINT-25, and MINT-31) clones were examined in 51 clear cell renal cell carcinomas (RCC). Results: By unsupervised hierarchical clustering analysis based on copy number alterations, clear cell RCCs were clustered into the two subclasses, clusters A (n =34) andB(n = 17). Copy number alterations were accumulated in cluster B. Loss of chromosome 3p and gain of 5q and 7 were frequent in both clusters A and B, whereas loss of 1p, 4, 9, 13q, and 14q was frequent only in cluster B. The average number of methylated CpG islands in cluster B was significantly higher than those in cluster A. Clear cell RCCs showing higher histologic grades, vascular involvement, renal vein tumor thrombi, and higher pathologic stages were accumulated in cluster B. The recurrence-free and overall survival rates of patients in cluster B were significantly lower than those of patients in cluster A. Multivariate analysis revealed that genetic clustering was a predictor of recurrence-free survival and was independent of histologic grade and pathologic stage. Conclusions: This genetic clustering of clear cell RCC is significantly associated with regional DNA hypermethylation and may become a prognostic indicator for patients with RCC.

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U2 - 10.1158/1078-0432.CCR-08-0443

DO - 10.1158/1078-0432.CCR-08-0443

M3 - Article

C2 - 18765545

AN - SCOPUS:53049094107

VL - 14

SP - 5531

EP - 5539

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 17

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