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Aberrant methylation of RASSF4/AD037 in nasopharyngeal carcinoma

Lillian Shuk-Nga Chow1, Kwok-Wai Lo, Joseph Kwong

  • 1Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, The Sir Y.K. Pao Center for Cancer, Prince of Wales Hospital, Shatin, Hong Kong SAR, China. snchow@cuhk.edu.hk

Oncology Reports
|September 18, 2004
PubMed

Insights

Epigenetic inactivation of RASSF4/AD037 and NORE1A is rare in nasopharyngeal carcinoma (NPC). These Ras-association domain family (RASSF) members may not be critical targets in NPC tumorigenesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The Ras-association domain family (RASSF) proteins, including RASSF1A, are implicated in cancer, with RASSF1A frequently inactivated by promoter hypermethylation in various human cancers.
  • Two less-studied RASSF family members, RASSF4/AD037 and NORE1, have been identified, and their roles in tumorigenesis require elucidation.
  • Nasopharyngeal carcinoma (NPC) is known for frequent RASSF1A inactivation, prompting an investigation into other RASSF members in this cancer.

Purpose of the Study:

  • To investigate the expression and methylation status of RASSF4/AD037 and NORE1 in nasopharyngeal carcinoma (NPC).
  • To determine if epigenetic inactivation of RASSF4/AD037 and NORE1 occurs in NPC and assess their potential role in tumorigenesis.

Main Methods:

  • Analysis of RASSF4/AD037 and NORE1 expression in NPC cell lines and xenografts.
  • Bisulfite sequencing to assess promoter methylation status of RASSF4/AD037 and NORE1A in NPC samples.
  • Treatment with a demethylating agent to evaluate the impact on RASSF4/AD037 expression.

Main Results:

  • RASSF4/AD037 expression was lost in 12.5% of NPC cell lines/xenografts, with dense promoter methylation identified and restored by demethylating agents.
  • Methylation of RASSF4/AD037 was found in 5% of primary NPC samples.
  • Partial methylation of NORE1A was detected in 37.5% of NPC cell lines/xenografts, but no aberrant methylation was observed in primary tumors, and expression was retained in all samples.

Conclusions:

  • Epigenetic inactivation of RASSF4/AD037 and NORE1A appears to be infrequent in nasopharyngeal carcinoma.
  • These findings suggest that RASSF4/AD037 and NORE1A may not be critical targets for gene inactivation during NPC tumorigenesis.

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