Aberrant promoter methylation profile of prostate cancers and its relationship to clinicopathological features

Riichiroh Maruyama, Shinichi Toyooka, Kiyomi O. Toyooka, Arvind K. Virmani, Sabine Zöchbauer-Müller, Alfredo J. Farinas, John D. Minna, John McConnell, Eugene P. Frenkel, Adi F. Gazdar

Research output: Contribution to journalArticle

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Abstract

Purpose: We investigated the aberrant methylation profile of prostate cancers and correlated the data with clinical findings. Experimental Design: Gene promoter methylation was analyzed in 101 prostate cancer samples. In addition, we analyzed 32 nonmalignant prostate tissue samples, which included 25 with benign disease, benign prostatic hypertrophy, or prostatitis, and 7 normal tissues adjacent to cancer. The methylation status of 10 genes was determined. The methylation index (MI) was calculated as a reflection of the methylated fraction of the genes examined. Results: Methylation percentages of the genes tested in prostate cancers were: RARβ, 53%; RASSF1A, 53% GSTP1, 36%; CDH13, 31%; APC, 27%; CDH1, 27%; FHIT, 15%; P16INK4A, 3%; DAPK, 1%; And MGMT, 0%. Methylation percentages in nonmalignant tissues were much lower. For clinicopathological correlations, we divided the cancer cases into low (6 or less) or high (7 or more) Gleason score (GS) groups, and into low (8 ng/ml or less) or high (greater than 8 ng/ml) preoperative serum prostate-specific antigen (PSA) groups. Methylation of RASSF1A, GSTP1, RARβ, and CDH13 genes was significantly more frequent in the high GS group than in the low GS group. Methylation of RASSF1A, CDH1, and GSTP1 genes was significantly more frequent in the high PSA group than in the low PSA group. The median MIS were significantly higher in the high GS and the high PSA groups. According to the Spearman rank-correlation test, there was significant correlation between MI and GS (coefficient = 0.43, P < 0.0001) and the preoperative serum PSA (coefficient = 0.37, P = 0.0003). Conclusions: Our results indicate that the methylation profile of prostate cancers correlates with clinicopathological features of poor prognosis.

Original languageEnglish (US)
Pages (from-to)514-519
Number of pages6
JournalClinical Cancer Research
Volume8
Issue number2
StatePublished - 2002

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Methylation
Prostatic Neoplasms
Neoplasm Grading
Prostate-Specific Antigen
Genes
Prostatitis
Prostatic Hyperplasia
Serum
Prostate
Neoplasms
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Maruyama, R., Toyooka, S., Toyooka, K. O., Virmani, A. K., Zöchbauer-Müller, S., Farinas, A. J., ... Gazdar, A. F. (2002). Aberrant promoter methylation profile of prostate cancers and its relationship to clinicopathological features. Clinical Cancer Research, 8(2), 514-519.

Aberrant promoter methylation profile of prostate cancers and its relationship to clinicopathological features. / Maruyama, Riichiroh; Toyooka, Shinichi; Toyooka, Kiyomi O.; Virmani, Arvind K.; Zöchbauer-Müller, Sabine; Farinas, Alfredo J.; Minna, John D.; McConnell, John; Frenkel, Eugene P.; Gazdar, Adi F.

In: Clinical Cancer Research, Vol. 8, No. 2, 2002, p. 514-519.

Research output: Contribution to journalArticle

Maruyama, R, Toyooka, S, Toyooka, KO, Virmani, AK, Zöchbauer-Müller, S, Farinas, AJ, Minna, JD, McConnell, J, Frenkel, EP & Gazdar, AF 2002, 'Aberrant promoter methylation profile of prostate cancers and its relationship to clinicopathological features', Clinical Cancer Research, vol. 8, no. 2, pp. 514-519.
Maruyama R, Toyooka S, Toyooka KO, Virmani AK, Zöchbauer-Müller S, Farinas AJ et al. Aberrant promoter methylation profile of prostate cancers and its relationship to clinicopathological features. Clinical Cancer Research. 2002;8(2):514-519.
Maruyama, Riichiroh ; Toyooka, Shinichi ; Toyooka, Kiyomi O. ; Virmani, Arvind K. ; Zöchbauer-Müller, Sabine ; Farinas, Alfredo J. ; Minna, John D. ; McConnell, John ; Frenkel, Eugene P. ; Gazdar, Adi F. / Aberrant promoter methylation profile of prostate cancers and its relationship to clinicopathological features. In: Clinical Cancer Research. 2002 ; Vol. 8, No. 2. pp. 514-519.
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abstract = "Purpose: We investigated the aberrant methylation profile of prostate cancers and correlated the data with clinical findings. Experimental Design: Gene promoter methylation was analyzed in 101 prostate cancer samples. In addition, we analyzed 32 nonmalignant prostate tissue samples, which included 25 with benign disease, benign prostatic hypertrophy, or prostatitis, and 7 normal tissues adjacent to cancer. The methylation status of 10 genes was determined. The methylation index (MI) was calculated as a reflection of the methylated fraction of the genes examined. Results: Methylation percentages of the genes tested in prostate cancers were: RARβ, 53{\%}; RASSF1A, 53{\%} GSTP1, 36{\%}; CDH13, 31{\%}; APC, 27{\%}; CDH1, 27{\%}; FHIT, 15{\%}; P16INK4A, 3{\%}; DAPK, 1{\%}; And MGMT, 0{\%}. Methylation percentages in nonmalignant tissues were much lower. For clinicopathological correlations, we divided the cancer cases into low (6 or less) or high (7 or more) Gleason score (GS) groups, and into low (8 ng/ml or less) or high (greater than 8 ng/ml) preoperative serum prostate-specific antigen (PSA) groups. Methylation of RASSF1A, GSTP1, RARβ, and CDH13 genes was significantly more frequent in the high GS group than in the low GS group. Methylation of RASSF1A, CDH1, and GSTP1 genes was significantly more frequent in the high PSA group than in the low PSA group. The median MIS were significantly higher in the high GS and the high PSA groups. According to the Spearman rank-correlation test, there was significant correlation between MI and GS (coefficient = 0.43, P < 0.0001) and the preoperative serum PSA (coefficient = 0.37, P = 0.0003). Conclusions: Our results indicate that the methylation profile of prostate cancers correlates with clinicopathological features of poor prognosis.",
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AU - Maruyama, Riichiroh

AU - Toyooka, Shinichi

AU - Toyooka, Kiyomi O.

AU - Virmani, Arvind K.

AU - Zöchbauer-Müller, Sabine

AU - Farinas, Alfredo J.

AU - Minna, John D.

AU - McConnell, John

AU - Frenkel, Eugene P.

AU - Gazdar, Adi F.

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N2 - Purpose: We investigated the aberrant methylation profile of prostate cancers and correlated the data with clinical findings. Experimental Design: Gene promoter methylation was analyzed in 101 prostate cancer samples. In addition, we analyzed 32 nonmalignant prostate tissue samples, which included 25 with benign disease, benign prostatic hypertrophy, or prostatitis, and 7 normal tissues adjacent to cancer. The methylation status of 10 genes was determined. The methylation index (MI) was calculated as a reflection of the methylated fraction of the genes examined. Results: Methylation percentages of the genes tested in prostate cancers were: RARβ, 53%; RASSF1A, 53% GSTP1, 36%; CDH13, 31%; APC, 27%; CDH1, 27%; FHIT, 15%; P16INK4A, 3%; DAPK, 1%; And MGMT, 0%. Methylation percentages in nonmalignant tissues were much lower. For clinicopathological correlations, we divided the cancer cases into low (6 or less) or high (7 or more) Gleason score (GS) groups, and into low (8 ng/ml or less) or high (greater than 8 ng/ml) preoperative serum prostate-specific antigen (PSA) groups. Methylation of RASSF1A, GSTP1, RARβ, and CDH13 genes was significantly more frequent in the high GS group than in the low GS group. Methylation of RASSF1A, CDH1, and GSTP1 genes was significantly more frequent in the high PSA group than in the low PSA group. The median MIS were significantly higher in the high GS and the high PSA groups. According to the Spearman rank-correlation test, there was significant correlation between MI and GS (coefficient = 0.43, P < 0.0001) and the preoperative serum PSA (coefficient = 0.37, P = 0.0003). Conclusions: Our results indicate that the methylation profile of prostate cancers correlates with clinicopathological features of poor prognosis.

AB - Purpose: We investigated the aberrant methylation profile of prostate cancers and correlated the data with clinical findings. Experimental Design: Gene promoter methylation was analyzed in 101 prostate cancer samples. In addition, we analyzed 32 nonmalignant prostate tissue samples, which included 25 with benign disease, benign prostatic hypertrophy, or prostatitis, and 7 normal tissues adjacent to cancer. The methylation status of 10 genes was determined. The methylation index (MI) was calculated as a reflection of the methylated fraction of the genes examined. Results: Methylation percentages of the genes tested in prostate cancers were: RARβ, 53%; RASSF1A, 53% GSTP1, 36%; CDH13, 31%; APC, 27%; CDH1, 27%; FHIT, 15%; P16INK4A, 3%; DAPK, 1%; And MGMT, 0%. Methylation percentages in nonmalignant tissues were much lower. For clinicopathological correlations, we divided the cancer cases into low (6 or less) or high (7 or more) Gleason score (GS) groups, and into low (8 ng/ml or less) or high (greater than 8 ng/ml) preoperative serum prostate-specific antigen (PSA) groups. Methylation of RASSF1A, GSTP1, RARβ, and CDH13 genes was significantly more frequent in the high GS group than in the low GS group. Methylation of RASSF1A, CDH1, and GSTP1 genes was significantly more frequent in the high PSA group than in the low PSA group. The median MIS were significantly higher in the high GS and the high PSA groups. According to the Spearman rank-correlation test, there was significant correlation between MI and GS (coefficient = 0.43, P < 0.0001) and the preoperative serum PSA (coefficient = 0.37, P = 0.0003). Conclusions: Our results indicate that the methylation profile of prostate cancers correlates with clinicopathological features of poor prognosis.

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