Hypermethylation of two consecutive tumor suppressor genes, BLU and RASSF1A, located at 3p21.3 in cervical neoplasias

Hung Cheng Lai, Ya Wen Lin, Cheng Chang Chang, Hui Chen Wang, Ta Wei Chu, Mu Hsien Yu, Tang Yuan Chu

研究成果: 雜誌貢獻文章

36 引文 (Scopus)

摘要

Objectives: Although initiated by human papillomavirus (HPV), cervical carcinogenesis demands other cofactors to shape its natural course. Epigenetic effects such as DNA methylation, are considered to contribute to carcinogenesis process. Methods: The methylation status of BLU and RASSF1A, as well as the HPV infection status, were assessed in a full spectrum of cervical neoplasia, including 45 low-grade squamous intraepithelial lesions (LSIL), 63 high-grade squamous intraepithelial lesions (HSIL), 107 squamous cell carcinomas (SCC), 23 adenocarcinomas (AC), and 44 normal control tissues. Results: The BLU was methylated in 76.9% of SCC, 57.4% of HSIL, 20.0% of LSIL and 12.5% of normal tissues (P <0.001). The RASSF1A was methylated in 15% of SCC, 17.5% of HSIL, but not in LSIL or normal tissues (P <0.001). In AC, 43.5% of patients showed BLU methylation and 26.1% RASSF1A methylation, significantly higher than the corresponding control frequencies of 12.5% (P = 0.005) and 0% (P = 0.001), respectively. There was an insignificant trend toward loss of BLU methylation with advancing clinical stages of SCC (84.8%, 67.7%, and 63.6% in stages I, II, and III/IV, respectively; P = 0.08). Patients with LSIL infected with high-risk HPV showed a higher rate of BLU methylation than those without HPV (38.8% vs 9.1%, respectively; P = 0.057). The methylation of RASSF1A was inversely related to HPV infection in patients with HSIL/SCC (P = 0.003). Conclusions: These results suggest that the methylation of BLU and RASSF1A genes is associated with cervical carcinogenesis, which could be clinically important in the future molecular screening of cervical neoplasia.

原文英語
頁(從 - 到)629-635
頁數7
期刊Gynecologic Oncology
104
發行號3
DOIs
出版狀態已發佈 - 三月 2007
對外發佈Yes

指紋

Tumor Suppressor Genes
Methylation
Squamous Cell Carcinoma
Neoplasms
Carcinogenesis
Papillomavirus Infections
Adenocarcinoma
Squamous Intraepithelial Lesions of the Cervix
DNA Methylation
Epigenomics
Genes

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology

引用此文

Hypermethylation of two consecutive tumor suppressor genes, BLU and RASSF1A, located at 3p21.3 in cervical neoplasias. / Lai, Hung Cheng; Lin, Ya Wen; Chang, Cheng Chang; Wang, Hui Chen; Chu, Ta Wei; Yu, Mu Hsien; Chu, Tang Yuan.

於: Gynecologic Oncology, 卷 104, 編號 3, 03.2007, p. 629-635.

研究成果: 雜誌貢獻文章

Lai, Hung Cheng ; Lin, Ya Wen ; Chang, Cheng Chang ; Wang, Hui Chen ; Chu, Ta Wei ; Yu, Mu Hsien ; Chu, Tang Yuan. / Hypermethylation of two consecutive tumor suppressor genes, BLU and RASSF1A, located at 3p21.3 in cervical neoplasias. 於: Gynecologic Oncology. 2007 ; 卷 104, 編號 3. 頁 629-635.
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title = "Hypermethylation of two consecutive tumor suppressor genes, BLU and RASSF1A, located at 3p21.3 in cervical neoplasias",
abstract = "Objectives: Although initiated by human papillomavirus (HPV), cervical carcinogenesis demands other cofactors to shape its natural course. Epigenetic effects such as DNA methylation, are considered to contribute to carcinogenesis process. Methods: The methylation status of BLU and RASSF1A, as well as the HPV infection status, were assessed in a full spectrum of cervical neoplasia, including 45 low-grade squamous intraepithelial lesions (LSIL), 63 high-grade squamous intraepithelial lesions (HSIL), 107 squamous cell carcinomas (SCC), 23 adenocarcinomas (AC), and 44 normal control tissues. Results: The BLU was methylated in 76.9{\%} of SCC, 57.4{\%} of HSIL, 20.0{\%} of LSIL and 12.5{\%} of normal tissues (P <0.001). The RASSF1A was methylated in 15{\%} of SCC, 17.5{\%} of HSIL, but not in LSIL or normal tissues (P <0.001). In AC, 43.5{\%} of patients showed BLU methylation and 26.1{\%} RASSF1A methylation, significantly higher than the corresponding control frequencies of 12.5{\%} (P = 0.005) and 0{\%} (P = 0.001), respectively. There was an insignificant trend toward loss of BLU methylation with advancing clinical stages of SCC (84.8{\%}, 67.7{\%}, and 63.6{\%} in stages I, II, and III/IV, respectively; P = 0.08). Patients with LSIL infected with high-risk HPV showed a higher rate of BLU methylation than those without HPV (38.8{\%} vs 9.1{\%}, respectively; P = 0.057). The methylation of RASSF1A was inversely related to HPV infection in patients with HSIL/SCC (P = 0.003). Conclusions: These results suggest that the methylation of BLU and RASSF1A genes is associated with cervical carcinogenesis, which could be clinically important in the future molecular screening of cervical neoplasia.",
keywords = "BLU, Cervical cancer, HPV, Methylation, RASSF1A",
author = "Lai, {Hung Cheng} and Lin, {Ya Wen} and Chang, {Cheng Chang} and Wang, {Hui Chen} and Chu, {Ta Wei} and Yu, {Mu Hsien} and Chu, {Tang Yuan}",
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T1 - Hypermethylation of two consecutive tumor suppressor genes, BLU and RASSF1A, located at 3p21.3 in cervical neoplasias

AU - Lai, Hung Cheng

AU - Lin, Ya Wen

AU - Chang, Cheng Chang

AU - Wang, Hui Chen

AU - Chu, Ta Wei

AU - Yu, Mu Hsien

AU - Chu, Tang Yuan

PY - 2007/3

Y1 - 2007/3

N2 - Objectives: Although initiated by human papillomavirus (HPV), cervical carcinogenesis demands other cofactors to shape its natural course. Epigenetic effects such as DNA methylation, are considered to contribute to carcinogenesis process. Methods: The methylation status of BLU and RASSF1A, as well as the HPV infection status, were assessed in a full spectrum of cervical neoplasia, including 45 low-grade squamous intraepithelial lesions (LSIL), 63 high-grade squamous intraepithelial lesions (HSIL), 107 squamous cell carcinomas (SCC), 23 adenocarcinomas (AC), and 44 normal control tissues. Results: The BLU was methylated in 76.9% of SCC, 57.4% of HSIL, 20.0% of LSIL and 12.5% of normal tissues (P <0.001). The RASSF1A was methylated in 15% of SCC, 17.5% of HSIL, but not in LSIL or normal tissues (P <0.001). In AC, 43.5% of patients showed BLU methylation and 26.1% RASSF1A methylation, significantly higher than the corresponding control frequencies of 12.5% (P = 0.005) and 0% (P = 0.001), respectively. There was an insignificant trend toward loss of BLU methylation with advancing clinical stages of SCC (84.8%, 67.7%, and 63.6% in stages I, II, and III/IV, respectively; P = 0.08). Patients with LSIL infected with high-risk HPV showed a higher rate of BLU methylation than those without HPV (38.8% vs 9.1%, respectively; P = 0.057). The methylation of RASSF1A was inversely related to HPV infection in patients with HSIL/SCC (P = 0.003). Conclusions: These results suggest that the methylation of BLU and RASSF1A genes is associated with cervical carcinogenesis, which could be clinically important in the future molecular screening of cervical neoplasia.

AB - Objectives: Although initiated by human papillomavirus (HPV), cervical carcinogenesis demands other cofactors to shape its natural course. Epigenetic effects such as DNA methylation, are considered to contribute to carcinogenesis process. Methods: The methylation status of BLU and RASSF1A, as well as the HPV infection status, were assessed in a full spectrum of cervical neoplasia, including 45 low-grade squamous intraepithelial lesions (LSIL), 63 high-grade squamous intraepithelial lesions (HSIL), 107 squamous cell carcinomas (SCC), 23 adenocarcinomas (AC), and 44 normal control tissues. Results: The BLU was methylated in 76.9% of SCC, 57.4% of HSIL, 20.0% of LSIL and 12.5% of normal tissues (P <0.001). The RASSF1A was methylated in 15% of SCC, 17.5% of HSIL, but not in LSIL or normal tissues (P <0.001). In AC, 43.5% of patients showed BLU methylation and 26.1% RASSF1A methylation, significantly higher than the corresponding control frequencies of 12.5% (P = 0.005) and 0% (P = 0.001), respectively. There was an insignificant trend toward loss of BLU methylation with advancing clinical stages of SCC (84.8%, 67.7%, and 63.6% in stages I, II, and III/IV, respectively; P = 0.08). Patients with LSIL infected with high-risk HPV showed a higher rate of BLU methylation than those without HPV (38.8% vs 9.1%, respectively; P = 0.057). The methylation of RASSF1A was inversely related to HPV infection in patients with HSIL/SCC (P = 0.003). Conclusions: These results suggest that the methylation of BLU and RASSF1A genes is associated with cervical carcinogenesis, which could be clinically important in the future molecular screening of cervical neoplasia.

KW - BLU

KW - Cervical cancer

KW - HPV

KW - Methylation

KW - RASSF1A

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