Promoter hypermethylation profile of ovarian epithelial neoplasms

Prakash B. Makarla, M. Hossein Saboorian, Raheela Ashfaq, Kiyomi O. Toyooka, Shinichi Toyooka, John D. Minna, Adi F. Gazdar, John O. Schorge

Research output: Contribution to journalArticle

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Abstract

Purpose: Ovarian carcinomas are believed to arise de novo from surface epithelium, but the actual molecular pathogenesis is unknown. The aim of this study was to compare the promoter hypermethylation profiles of ovarian epithelial neoplasms to better understand the role of epigenetic silencing in carcinogenesis. Experimental Design: We analyzed the DNA promoter methylation status of eight tumor suppressor and cancer-related genes (p16, RARβ, E-cadherin, H-cadherin, APC, GSTP1, MGMT, RASSF1A) in 23 benign cystadenomas, 23 low malignant potential (LMP) tumors, and 23 invasive carcinomas by methylation-specific PCR. Results: Benign cystadenomas exhibited promoter hypermethylation in only two genes, p16 (13%) and E-cadherin (13%). LMP tumors also showed p16 (22%) and E-cadherin (17%) methylation, in addition to RARβ (9%) and H-cadherin (4%). All eight genes were hypermethylated in invasive cancers at a frequency of 9% to 30%. The mean methylation index was highest in invasive tumors [0.20 versus 0.065 (LMP) and 0.033 (cystadenomas); P = 0.001]. Promoter methylation of at least one gene was most commonly observed among invasive cancers [78% versus 44% (LMP; P = 0.03) and 26% (cystadenomas; P = 0.0009)]. Three genes exhibited higher methylation frequencies in invasive tumors: RASSFIA (30% versus 0%; P = 0.0002), H-cadherin (22% versus 2%; P = 0.013), and APC (22% versus 0%; P = 0.003). Conclusions: Promoter hypermethylation is a frequent epigenetic event that occurs most commonly in invasive epithelial ovarian carcinomas. The profile of aberrant methylation suggests that an accumulation of events at specific genes may trigger malignant transformation of some benign cystadenomas and LMP tumors.

Original languageEnglish
Pages (from-to)5365-5369
Number of pages5
JournalClinical Cancer Research
Volume11
Issue number15
DOIs
Publication statusPublished - Aug 1 2005
Externally publishedYes

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Glandular and Epithelial Neoplasms
Ovarian Neoplasms
Cystadenoma
Methylation
Neoplasms
Cadherins
Carcinoma
Epigenomics
Genes
p16 Genes
DNA Methylation
Tumor Suppressor Genes
Carcinogenesis
Research Design
Epithelium
Polymerase Chain Reaction
H-cadherin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Makarla, P. B., Saboorian, M. H., Ashfaq, R., Toyooka, K. O., Toyooka, S., Minna, J. D., ... Schorge, J. O. (2005). Promoter hypermethylation profile of ovarian epithelial neoplasms. Clinical Cancer Research, 11(15), 5365-5369. https://doi.org/10.1158/1078-0432.CCR-04-2455

Promoter hypermethylation profile of ovarian epithelial neoplasms. / Makarla, Prakash B.; Saboorian, M. Hossein; Ashfaq, Raheela; Toyooka, Kiyomi O.; Toyooka, Shinichi; Minna, John D.; Gazdar, Adi F.; Schorge, John O.

In: Clinical Cancer Research, Vol. 11, No. 15, 01.08.2005, p. 5365-5369.

Research output: Contribution to journalArticle

Makarla, PB, Saboorian, MH, Ashfaq, R, Toyooka, KO, Toyooka, S, Minna, JD, Gazdar, AF & Schorge, JO 2005, 'Promoter hypermethylation profile of ovarian epithelial neoplasms', Clinical Cancer Research, vol. 11, no. 15, pp. 5365-5369. https://doi.org/10.1158/1078-0432.CCR-04-2455
Makarla PB, Saboorian MH, Ashfaq R, Toyooka KO, Toyooka S, Minna JD et al. Promoter hypermethylation profile of ovarian epithelial neoplasms. Clinical Cancer Research. 2005 Aug 1;11(15):5365-5369. https://doi.org/10.1158/1078-0432.CCR-04-2455
Makarla, Prakash B. ; Saboorian, M. Hossein ; Ashfaq, Raheela ; Toyooka, Kiyomi O. ; Toyooka, Shinichi ; Minna, John D. ; Gazdar, Adi F. ; Schorge, John O. / Promoter hypermethylation profile of ovarian epithelial neoplasms. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 15. pp. 5365-5369.
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abstract = "Purpose: Ovarian carcinomas are believed to arise de novo from surface epithelium, but the actual molecular pathogenesis is unknown. The aim of this study was to compare the promoter hypermethylation profiles of ovarian epithelial neoplasms to better understand the role of epigenetic silencing in carcinogenesis. Experimental Design: We analyzed the DNA promoter methylation status of eight tumor suppressor and cancer-related genes (p16, RARβ, E-cadherin, H-cadherin, APC, GSTP1, MGMT, RASSF1A) in 23 benign cystadenomas, 23 low malignant potential (LMP) tumors, and 23 invasive carcinomas by methylation-specific PCR. Results: Benign cystadenomas exhibited promoter hypermethylation in only two genes, p16 (13{\%}) and E-cadherin (13{\%}). LMP tumors also showed p16 (22{\%}) and E-cadherin (17{\%}) methylation, in addition to RARβ (9{\%}) and H-cadherin (4{\%}). All eight genes were hypermethylated in invasive cancers at a frequency of 9{\%} to 30{\%}. The mean methylation index was highest in invasive tumors [0.20 versus 0.065 (LMP) and 0.033 (cystadenomas); P = 0.001]. Promoter methylation of at least one gene was most commonly observed among invasive cancers [78{\%} versus 44{\%} (LMP; P = 0.03) and 26{\%} (cystadenomas; P = 0.0009)]. Three genes exhibited higher methylation frequencies in invasive tumors: RASSFIA (30{\%} versus 0{\%}; P = 0.0002), H-cadherin (22{\%} versus 2{\%}; P = 0.013), and APC (22{\%} versus 0{\%}; P = 0.003). Conclusions: Promoter hypermethylation is a frequent epigenetic event that occurs most commonly in invasive epithelial ovarian carcinomas. The profile of aberrant methylation suggests that an accumulation of events at specific genes may trigger malignant transformation of some benign cystadenomas and LMP tumors.",
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AU - Makarla, Prakash B.

AU - Saboorian, M. Hossein

AU - Ashfaq, Raheela

AU - Toyooka, Kiyomi O.

AU - Toyooka, Shinichi

AU - Minna, John D.

AU - Gazdar, Adi F.

AU - Schorge, John O.

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N2 - Purpose: Ovarian carcinomas are believed to arise de novo from surface epithelium, but the actual molecular pathogenesis is unknown. The aim of this study was to compare the promoter hypermethylation profiles of ovarian epithelial neoplasms to better understand the role of epigenetic silencing in carcinogenesis. Experimental Design: We analyzed the DNA promoter methylation status of eight tumor suppressor and cancer-related genes (p16, RARβ, E-cadherin, H-cadherin, APC, GSTP1, MGMT, RASSF1A) in 23 benign cystadenomas, 23 low malignant potential (LMP) tumors, and 23 invasive carcinomas by methylation-specific PCR. Results: Benign cystadenomas exhibited promoter hypermethylation in only two genes, p16 (13%) and E-cadherin (13%). LMP tumors also showed p16 (22%) and E-cadherin (17%) methylation, in addition to RARβ (9%) and H-cadherin (4%). All eight genes were hypermethylated in invasive cancers at a frequency of 9% to 30%. The mean methylation index was highest in invasive tumors [0.20 versus 0.065 (LMP) and 0.033 (cystadenomas); P = 0.001]. Promoter methylation of at least one gene was most commonly observed among invasive cancers [78% versus 44% (LMP; P = 0.03) and 26% (cystadenomas; P = 0.0009)]. Three genes exhibited higher methylation frequencies in invasive tumors: RASSFIA (30% versus 0%; P = 0.0002), H-cadherin (22% versus 2%; P = 0.013), and APC (22% versus 0%; P = 0.003). Conclusions: Promoter hypermethylation is a frequent epigenetic event that occurs most commonly in invasive epithelial ovarian carcinomas. The profile of aberrant methylation suggests that an accumulation of events at specific genes may trigger malignant transformation of some benign cystadenomas and LMP tumors.

AB - Purpose: Ovarian carcinomas are believed to arise de novo from surface epithelium, but the actual molecular pathogenesis is unknown. The aim of this study was to compare the promoter hypermethylation profiles of ovarian epithelial neoplasms to better understand the role of epigenetic silencing in carcinogenesis. Experimental Design: We analyzed the DNA promoter methylation status of eight tumor suppressor and cancer-related genes (p16, RARβ, E-cadherin, H-cadherin, APC, GSTP1, MGMT, RASSF1A) in 23 benign cystadenomas, 23 low malignant potential (LMP) tumors, and 23 invasive carcinomas by methylation-specific PCR. Results: Benign cystadenomas exhibited promoter hypermethylation in only two genes, p16 (13%) and E-cadherin (13%). LMP tumors also showed p16 (22%) and E-cadherin (17%) methylation, in addition to RARβ (9%) and H-cadherin (4%). All eight genes were hypermethylated in invasive cancers at a frequency of 9% to 30%. The mean methylation index was highest in invasive tumors [0.20 versus 0.065 (LMP) and 0.033 (cystadenomas); P = 0.001]. Promoter methylation of at least one gene was most commonly observed among invasive cancers [78% versus 44% (LMP; P = 0.03) and 26% (cystadenomas; P = 0.0009)]. Three genes exhibited higher methylation frequencies in invasive tumors: RASSFIA (30% versus 0%; P = 0.0002), H-cadherin (22% versus 2%; P = 0.013), and APC (22% versus 0%; P = 0.003). Conclusions: Promoter hypermethylation is a frequent epigenetic event that occurs most commonly in invasive epithelial ovarian carcinomas. The profile of aberrant methylation suggests that an accumulation of events at specific genes may trigger malignant transformation of some benign cystadenomas and LMP tumors.

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