Protocadherin PCDH10, involved in tumor progression, is a frequent and early target of promoter hypermethylation in cervical cancer
Article first published online: 13 AUG 2009
Copyright © 2009 Wiley-Liss, Inc.
Genes, Chromosomes and Cancer
Volume 48, Issue 11, pages 983–992, November 2009
How to Cite
Narayan, G., Scotto, L., Neelakantan, V., Kottoor, S. H., Wong, A. H. Y., Loke, S.-L., Mansukhani, M., Pothuri, B., Wright, J. D., Kaufmann, A. M., Schneider, A., Arias-Pulido, H., Tao, Q. and Murty, V. V. (2009), Protocadherin PCDH10, involved in tumor progression, is a frequent and early target of promoter hypermethylation in cervical cancer. Genes Chromosom. Cancer, 48: 983–992. doi: 10.1002/gcc.20703
- Issue published online: 10 SEP 2009
- Article first published online: 13 AUG 2009
- Manuscript Accepted: 20 JUL 2009
- Manuscript Received: 20 MAR 2009
- National Institutes of Health. Grant Number: CA095647
Cervical cancer (CC) is the second most common cancer in women. Currently, no tractable molecular-based therapeutic targets exist for patients with invasive CC and no predictive markers of risk assessment for progression of precancerous lesions are identified. New molecular insights into CC pathogenesis are urgently needed. Towards this goal, we first determined the copy number alterations of chromosome 4 and then examined the role of PCDH10 mapped to 4q28 as a candidate tumor suppressor gene. We identified monosomy 4 in 47% of 81 invasive CC studied by SNP array and found that 91% of 130 invasive CC harboring methylation in the promoter region of the PCDH10 gene. We then showed that aberrant promoter hypermethylation of PCDH10 is associated with downregulation of gene expression and cell lines exposed to demethylating agent resulted in profound reactivated gene expression. We also showed that the promoter methylation in the PCDH10 gene occurs at an earliest identifiable stage of low-grade squamous intraepithelial lesion. Our studies demonstrate that inactivation of PCDH10 may be a critical event in CC progression and form a potentially useful therapeutic target for CC. © 2009 Wiley-Liss, Inc.