Premium
Protocadherin PCDH10, involved in tumor progression, is a frequent and early target of promoter hypermethylation in cervical cancer
Author(s) -
Narayan Gopeshwar,
Scotto Luigi,
Neelakantan Vijayalakshmi,
Kottoor Sherine H.,
Wong Ada Ho Yan,
Loke SheeLoong,
Mansukhani Mahesh,
Pothuri Bhavana,
Wright Jason D.,
Kaufmann Andreas M.,
Schneider Achim,
AriasPulido Hugo,
Tao Qian,
Murty Vundavalli V.
Publication year - 2009
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20703
Subject(s) - protocadherin , dna methylation , cancer research , epigenetics , biology , promoter , demethylating agent , gene , methylation , cancer , gene expression , genetics , cell , cadherin
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.