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

Research output: Contribution to journalArticle

35 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)629-635
Number of pages7
JournalGynecologic Oncology
Volume104
Issue number3
DOIs
Publication statusPublished - Mar 2007
Externally publishedYes

Fingerprint

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

Keywords

  • BLU
  • Cervical cancer
  • HPV
  • Methylation
  • RASSF1A

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology

Cite this

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.

In: Gynecologic Oncology, Vol. 104, No. 3, 03.2007, p. 629-635.

Research output: Contribution to journalArticle

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. In: Gynecologic Oncology. 2007 ; Vol. 104, No. 3. pp. 629-635.
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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.",
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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.

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