Early Detection and Diagnosis

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Identification of novel DNA methylation markers in cervical cancer†

  1. Hung-Cheng Lai1,2,‡,*,
  2. Ya-Wen Lin2,3,
  3. Tim H.M. Huang4,
  4. Pearlly Yan4,
  5. Rui-Lan Huang1,
  6. Hui-Chen Wang1,
  7. Joseph Liu4,
  8. Michael W.Y. Chan5,
  9. Tang-Yuan Chu6,
  10. Chien-An Sun7,
  11. Cheng-Chang Chang1,
  12. Mu-Hsien Yu1

Article first published online: 8 APR 2008

DOI: 10.1002/ijc.23519

Issue

International Journal of Cancer

International Journal of Cancer

Volume 123, Issue 1, pages 161–167, 1 July 2008

Additional Information

How to Cite

Lai, H.-C., Lin, Y.-W., Huang, T. H.M., Yan, P., Huang, R.-L., Wang, H.-C., Liu, J., Chan, M. W.Y., Chu, T.-Y., Sun, C.-A., Chang, C.-C. and Yu, M.-H. (2008), Identification of novel DNA methylation markers in cervical cancer. Int. J. Cancer, 123: 161–167. doi: 10.1002/ijc.23519

Author Information

  1. 1

    Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taipei, Taiwan, Republic of China

  2. 2

    Laboratory of Epigenetics, National Defense Medical Center, Taipei, Taiwan, Republic of China

  3. 3

    Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China

  4. 4

    Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH

  5. 5

    Department of Life Science, National Chung Cheng University, Min-Hsiung Chia-Yi, Taiwan, Republic of China

  6. 6

    Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan, Republic of China

  7. 7

    School of Public Health, National Defense Medical Center, Taipei, Taiwan, Republic of China

  1. ‡

    Fax: +886-2-8792-7199.

*Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, 5F, 325, Sec 2, Cheng-Gong Rd., Neihu District, Taipei City 114, Taiwan, Republic of China

  1. †

    The application for patents using these DNA sequences in cancer screening is in processing.

Publication History

  1. Issue published online: 24 APR 2008
  2. Article first published online: 8 APR 2008
  3. Manuscript Accepted: 23 JAN 2008
  4. Manuscript Received: 19 JAN 2008

Funded by

  • Tri-Service General Hospital. Grant Number: TSGH-C96-2-S01∼4
  • National Science Council, Republic of China. Grant Numbers: NSC95-2622-B-016-001, NSC95-2314-B-016-058-MY2
  • C.Y. Chai Foundation for Advancement of Education, Sciences and Medicine
  • Human Medical Research Foundation. Grant Number: B962114-1

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Keywords:

  • cervical cancer;
  • epigenetics;
  • hpv;
  • methylation;
  • microarray

Abstract

Testing for DNA methylation has potential in cancer screening. Most previous studies of DNA methylation in cervical cancer used a candidate gene approach. The aim our study was to identify novel genes that are methylated in cervical cancers and to test their potential in clinical applications. We did a differential methylation hybridization using a CpG island (CGI) microarray containing 8640 CGI tags to uncover methylated genes in squamous cell carcinomas (SCC) of the uterine cervix. Pooled DNA from cancer tissues and normal cervical swabs were used for comparison. Methylation-specific polymerase chain reaction, bisulfite sequencing and reverse transcription polymerase chain reaction were used to confirm the methylation status in cell lines, normal cervices (n = 45), low-grade lesions (n = 45), high-grade lesions (HSIL; n = 58) and invasive squamous cell carcinomas (SCC; n = 22 from swabs and n = 109 from tissues). Human papillomavirus (HPV) was detected using reverse line blots. We reported 6 genes (SOX1, PAX1, LMX1A, NKX6-1, WT1 and ONECUT1) more frequently methylated in SCC tissues (81.5, 94.4, 89.9, 80.4, 77.8 and 20.4%, respectively) than in their normal controls (2.2, 0, 6.7, 11.9, 11.1 and 0%, respectively; p < 0.0001). Parallel testing of HPV and PAX1 methylation in cervical swabs confers an improved sensitivity than HPV testing alone (80% vs. 66%) without compromising specificity (63% vs. 64%) for HSIL/SCC. Testing PAX1 methylation marker alone, the specificity for HSIL/SCC is 99%. The analysis of these novel DNA methylations may be a promising approach for the screening of cervical cancers. © 2008 Wiley-Liss, Inc.

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